notebook.community

Edit and run



In [3]:

    
def load_gene_names():
    ret = set()
    syns = {}

    with open('genenames.txt') as f:
        c = 0
        for l in f:
            c += 1
            if c == 1:
                header = l.split('\t')
                syn_index = header.index('Synonyms')
                symb_index = header.index('Previous Symbols')
                continue
                
            ls = l.split('\t')
            gene = ls[1]
            ret.add(gene)
            this_syn = [x.strip() for x in ls[syn_index].split(',')]
            for x in this_syn:
                syns[x] = gene
            
            symbols = [x.strip() for x in ls[symb_index].split(',')]
            for x in symbols:
                syns[x] = gene
            
            
    return {x: None for x in ret}, syns

stop = {
    '2': None,
    'T': None,
    'B': None,
}

def check_gene_name(x):
    
    if x in stop:
        return None
    
    if x in genenames:
        if not 'realnames' in stats:
            stats['realnames'] = 0
        stats['realnames'] += 1
        
        return x
    
    if x in genesyns:
        
        if not 'syns' in stats:
            stats['syns'] = 0
        stats['syns'] += 1
        
        return genesyns[x]
    
    extra_synonyms = {
        # Found : Real
        'FXII': 'F12',
    }
    
    if x in extra_synonyms:
        return extra_synonyms[x]
    
    if x.lower() in ['mitochondrial', 'mtdna']:
        
        if not 'mitochondrial' in stats:
            stats['mitochondrial'] = 0
        stats['mitochondrial'] += 1
        
        return 'mtdna'
    
    return None



In [4]:

    
genenames, genesyns = load_gene_names()



In [9]:

    
genenames['BRCA2']



In [10]:

    
genesyns['HPRT']









    



---------------------------------------------------------------------------
KeyError                                  Traceback (most recent call last)
<ipython-input-10-511b85dce355> in <module>()
----> 1 genesyns['HPRT']

KeyError: 'HPRT'



In [18]:

    
import re
import json
import codecs

stats = {}

def gen_abstracts(filename, per=100):
    abstract_counter = 0
    hgvs_counter = 0
    with open(filename) as f:
        for l in f:
                        
            data = json.loads(l)
            for result in data['resultList']['result']:
                
                if not 'pubmedcounter' in stats:
                    stats['pubmedcounter'] = 0
                stats['pubmedcounter'] += 1
                
                if 'abstractText'in result:
                    abstract = result['abstractText']
                    abstract_counter += 1
                    if abstract_counter % per == 0:
                        print ('Abstract counter:', abstract_counter)
                        
                    if not 'abstractcounter' in stats:
                        stats['abstractcounter'] = 0
                    stats['abstractcounter'] += 1
                        
                    #if 'NM_' in abstract:
                    #    print (abstract)
                    #    assert False
                    yield abstract
                else:
                    if not 'noabstract' in stats:
                        stats['noabstract'] = 0
                    stats['noabstract'] += 1

def gen_hgvs(filename):
    hgvs_counter = 0
    
    for abstract in gen_abstracts(filename):
        
        transcripts = get_transcripts(abstract)
        
        for hgvs in gen_hgvs_2(abstract):
            hgvs_counter += 1

            if hgvs_counter % 100 == 0:
                print ('HGVS FOUND:', hgvs_counter)
            
            gene = get_gene_names(abstract, hgvs[1])
            
            yield abstract, gene, ''.join(hgvs), transcripts

def get_gene_names(abstract, hgvs):
    pos = abstract.index(hgvs)
    
    before = abstract[:pos]
    after = abstract[pos+len(hgvs):]
    
    #Check before
    before = before.split()[::-1]
    before = [noparenthesis(x) for x in before]
    
    for word in before:
        name = check_gene_name(word)
        if name:
            return name
    
    #Check after
    after = [noparenthesis(x) for x in after.split()]
    for word in after:
        name = check_gene_name(word)
        if name:
            return name
    
    if not 'no_gene' in stats:
        stats['no_gene'] = 0
        
    stats['no_gene'] += 1
    
    #print abstract
    #print hgvs
    
    #if stats['no_gene'] > 1:
    #    assert False
    return None

def gen_hgvs_2(abstract):
    #245 A>
    #found = re.findall(r'(.{1,100})([\d]+[\s]*[ACGT]+[\s]*>)(.{1,100})',abstract, re.UNICODE)
    found = re.findall(r'[\d]+[\s]*[ACGT]+[\s]*>',abstract, re.UNICODE)
    
    if not found:
        if not 'nohgvs' in stats:
            stats['nohgvs'] = 0
        stats['nohgvs'] += 1
    
    for f in found:
        start = abstract.index(f)
        before = abstract[:start]
        after = abstract[start+len(f):]
        
        # We do not want any HGVS before and after the one that we found
        before = before.replace('>','')
        after = after.replace('>', '')

        yield before, f, after
    

def get_transcripts(text):
    return re.findall(r'[A-Z][A-Z]_[\d]{4,15}\.?[\d]*', text, re.UNICODE)
        
def nowhite(p):
    return re.sub(r'[\s]', '', p, flags=re.UNICODE)

def noparenthesis(p):
    return re.sub(r'[\(\),\.\:]', '', p, flags=re.UNICODE)

def post_process(hgvs):

    s = None
    
    if not s:
        # c.6348+1G>A
        s = re.search(r'[CcGgpP][\s]*\.[\s]*[\d]+[\s]*[\+\-][\s]*[\d]+[\s]*[ACGT]+[\s]*>[\s]*[ACGT]+', hgvs, re.UNICODE)
    
    if not s:
        # c.969C > A
        s = re.search(r'[CcGgpPm][\s]*\.[\s]*[\d]+[\s]*[ACGT][\s]*>[\s]*[ACGTS]+', hgvs, re.UNICODE)
    
    if not s:
        # 236G > A
        s = re.search(r'[\d]+[\s]*[ACGT]+[\s]*>[\s]*[ACGT]+', hgvs, re.UNICODE)
    
    if not s:
        # c.743C > del 
        s = re.search(r'[cCgGpP]\.[\d]+[ACGT]+[\s]*>[\s]*del', hgvs, re.UNICODE)
    
    #print ('=====')
    if s:
        result = nowhite(s.group(0))
        #print (hgvs)
        #print (result)
        return result
    else:
        #print (hgvs)
        #assert False
        
        if not 'noparsehgvs' in stats:
            stats['noparsehgvs'] = 0
        stats['noparsehgvs'] += 1
        
        return None
        
        
def do_1():
    output_fn = 'parsed_abstracts.json'
    output_f = codecs.open(output_fn, 'w', 'utf-8')
    records = 0
    for abstract, gene, hgvs, transcripts in gen_hgvs('abstracts.json'):
        hgvs = post_process(hgvs)
        if hgvs is None:
            continue

        
        records += 1
        
        #if records <8:
        #    continue
        
        if records > 100:
            break
        
        to_save = {
            'abstract': abstract,
            'gene': gene,
            'hgvs': hgvs,
            'transcripts': transcripts,
            'record': records
        }
        
        #print gene, hgvs, transcripts
        if False:
            output_f.write('=========== {} ================\n'.format(records))
            output_f.write(abstract + '\n')
            output_f.write('GENE:' + gene + '\n')
            output_f.write('HGVS:'+ hgvs + '\n')
            output_f.write('Transcripts:' + str(transcripts) + '\n')
        if True:
            print 'Record:', records
            json.dump(to_save, output_f)
            output_f.write('\n')
            output_f.flush()
               
    output_f.close()
    print 'Generated:', output_fn
    
    with open('stats.json', 'w') as f:
        json.dump(stats, f)
    print 'Generated:', 'stats.json'

def do_2():
    counter={}
    for abstract in gen_abstracts('abstracts.json', per=10000):
        for tr in ['NT_', 'NG_', 'NC_']:
            if tr in abstract:
                #print '=====  {}  ======'.format(tr)
                if not tr in counter:
                    counter[tr] = []
                    
                counter[tr].append(abstract)
                #print abstract
                #assert False
                
    #print (counter)
    return counter
        
do_1()
#do_2()









    



Record: 1
Record: 2
Record: 3
Record: 4
Record: 5
Record: 6
Record: 7
Record: 8
Record: 9
Record: 10
Record: 11
Record: 12
Record: 13
Record: 14
Record: 15
Record: 16
Record: 17
Record: 18
Record: 19
Record: 20
Record: 21
Record: 22
Record: 23
Record: 24
Record: 25
Record: 26
Record: 27
Record: 28
Record: 29
Record: 30
Record: 31
Record: 32
Record: 33
Record: 34
Record: 35
Record: 36
Record: 37
Record: 38
Record: 39
Record: 40
Record: 41
Record: 42
Record: 43
Record: 44
Record: 45
Record: 46
Record: 47
Record: 48
Record: 49
Record: 50
Record: 51
Record: 52
Record: 53
Record: 54
Record: 55
Record: 56
Record: 57
Record: 58
Record: 59
Record: 60
Record: 61
Record: 62
Record: 63
Record: 64
Record: 65
Record: 66
Record: 67
('Abstract counter:', 100)
Record: 68
Record: 69
Record: 70
Record: 71
Record: 72
Record: 73
Record: 74
Record: 75
Record: 76
Record: 77
Record: 78
Record: 79
Record: 80
Record: 81
Record: 82
Record: 83
Record: 84
Record: 85
Record: 86
Record: 87
Record: 88
Record: 89
Record: 90
Record: 91
Record: 92
Record: 93
Record: 94
Record: 95
Record: 96
Record: 97
Record: 98
Record: 99
('Abstract counter:', 200)
('HGVS FOUND:', 100)
Record: 100
Generated: parsed_abstracts.json
Generated: stats.json



In [1]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'SERPINF1:c.1067' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
SERPINF1:c.1067	CCDS11012 (protein_coding)	SERPINF1	+	chr17:g.1680550T/c.1067T/.	inside_[cds_in_exon_7]	source=CCDS



In [36]:

    
genenames['LIS1']









    



---------------------------------------------------------------------------
KeyError                                  Traceback (most recent call last)
<ipython-input-36-6a6307ca66fe> in <module>()
----> 1 genenames['LIS1']

KeyError: 'LIS1'



In [11]:

    
counter = do_2()









    



('Abstract counter:', 10000)
('Abstract counter:', 20000)
('Abstract counter:', 30000)
('Abstract counter:', 40000)
('Abstract counter:', 50000)
('Abstract counter:', 60000)
('Abstract counter:', 70000)
('Abstract counter:', 80000)
('Abstract counter:', 90000)
('Abstract counter:', 100000)
('Abstract counter:', 110000)
('Abstract counter:', 120000)
('Abstract counter:', 130000)
('Abstract counter:', 140000)
('Abstract counter:', 150000)
('Abstract counter:', 160000)
('Abstract counter:', 170000)
('Abstract counter:', 180000)
('Abstract counter:', 190000)
('Abstract counter:', 200000)
('Abstract counter:', 210000)
('Abstract counter:', 220000)
('Abstract counter:', 230000)
('Abstract counter:', 240000)
('Abstract counter:', 250000)
('Abstract counter:', 260000)
('Abstract counter:', 270000)
('Abstract counter:', 280000)
('Abstract counter:', 290000)
('Abstract counter:', 300000)
('Abstract counter:', 310000)
('Abstract counter:', 320000)
('Abstract counter:', 330000)
('Abstract counter:', 340000)
('Abstract counter:', 350000)
('Abstract counter:', 360000)
('Abstract counter:', 370000)
('Abstract counter:', 380000)
('Abstract counter:', 390000)
('Abstract counter:', 400000)
('Abstract counter:', 410000)
('Abstract counter:', 420000)
('Abstract counter:', 430000)
('Abstract counter:', 440000)
('Abstract counter:', 450000)
('Abstract counter:', 460000)
('Abstract counter:', 470000)
('Abstract counter:', 480000)
('Abstract counter:', 490000)
('Abstract counter:', 500000)
('Abstract counter:', 510000)
('Abstract counter:', 520000)
('Abstract counter:', 530000)
('Abstract counter:', 540000)
('Abstract counter:', 550000)
('Abstract counter:', 560000)
('Abstract counter:', 570000)
('Abstract counter:', 580000)
('Abstract counter:', 590000)
('Abstract counter:', 600000)
('Abstract counter:', 610000)
('Abstract counter:', 620000)
('Abstract counter:', 630000)
('Abstract counter:', 640000)
('Abstract counter:', 650000)
('Abstract counter:', 660000)
('Abstract counter:', 670000)
('Abstract counter:', 680000)
('Abstract counter:', 690000)
('Abstract counter:', 700000)
('Abstract counter:', 710000)
('Abstract counter:', 720000)
('Abstract counter:', 730000)
('Abstract counter:', 740000)
('Abstract counter:', 750000)
('Abstract counter:', 760000)
('Abstract counter:', 770000)
('Abstract counter:', 780000)
('Abstract counter:', 790000)
('Abstract counter:', 800000)
('Abstract counter:', 810000)
('Abstract counter:', 820000)
('Abstract counter:', 830000)
('Abstract counter:', 840000)
('Abstract counter:', 850000)
('Abstract counter:', 860000)
('Abstract counter:', 870000)
('Abstract counter:', 880000)
('Abstract counter:', 890000)
('Abstract counter:', 900000)
('Abstract counter:', 910000)



In [12]:

    
with open('nt_ng_abstracts.json', 'w') as f:
    json.dump(counter, f)



In [13]:

    
for x,y in counter.iteritems():
    print x, len(y)









    



NG_ 52
NT_ 24
NC_ 68



In [1]:

    
from MutationInfo import MutationInfo as MI









    



/home/user/mutationinfo/localpython/lib/python2.7/site-packages/psycopg2-2.7.4-py2.7-linux-x86_64.egg/psycopg2/__init__.py:144: UserWarning: The psycopg2 wheel package will be renamed from release 2.8; in order to keep installing from binary please use "pip install psycopg2-binary" instead. For details see: <http://initd.org/psycopg/docs/install.html#binary-install-from-pypi>.
  """)



In [2]:

    
mi = MI()









    



WARNING dbfile.open_index: Falling back to hash index: unable to import bsddb






    



WARNING:pygr-log:Falling back to hash index: unable to import bsddb

RUN_1

Run with: /home/user/mutationinfo/localpython/bin/python run_1.py



In [21]:

    
%%writefile run_1.py
# -*- coding: utf-8 -*-

def load_gene_names():
    ret = set()
    syns = {}

    with open('genenames.txt') as f:
        c = 0
        for l in f:
            c += 1
            if c == 1:
                header = l.split('\t')
                syn_index = header.index('Synonyms')
                symb_index = header.index('Previous Symbols')
                continue
                
            ls = l.split('\t')
            gene = ls[1]
            ret.add(gene)
            this_syn = [x.strip() for x in ls[syn_index].split(',')]
            for x in this_syn:
                syns[x] = gene
            
            symbols = [x.strip() for x in ls[symb_index].split(',')]
            for x in symbols:
                syns[x] = gene
            
            
    return {x: None for x in ret}, syns

stop = {
    '2': None,
    'T': None,
    'B': None,
}

def check_gene_name(x):
    
    if x in stop:
        return None
    
    if x in genenames:
        if not 'realnames' in stats:
            stats['realnames'] = 0
        stats['realnames'] += 1
        
        return x
    
    if x in genesyns:
        
        if not 'syns' in stats:
            stats['syns'] = 0
        stats['syns'] += 1
        
        return genesyns[x]
    
    extra_synonyms = {
        # Found : Real
        'FXII': 'F12',
    }
    
    if x in extra_synonyms:
        return extra_synonyms[x]
    
    if x.lower() in ['mitochondrial', 'mtdna']:
        
        if not 'mitochondrial' in stats:
            stats['mitochondrial'] = 0
        stats['mitochondrial'] += 1
        
        return 'mtdna'
    
    return None

###################################
genenames, genesyns = load_gene_names()

import re
import gzip
import json
import codecs

stats = {}

def gen_abstracts(filename, per=100):
    abstract_counter = 0
    hgvs_counter = 0
    with gzip.open(filename, 'rt') as f:
        for l in f:
                        
            data = json.loads(l)
            for result in data['resultList']['result']:
                
                if not 'pubmedcounter' in stats:
                    stats['pubmedcounter'] = 0
                stats['pubmedcounter'] += 1
                
                if 'abstractText'in result:
                    abstract = result['abstractText']
                    abstract_counter += 1
                    if abstract_counter % per == 0:
                        print ('Abstract counter:', abstract_counter)
                        
                    if not 'abstractcounter' in stats:
                        stats['abstractcounter'] = 0
                    stats['abstractcounter'] += 1
                        
                    #if 'NM_' in abstract:
                    #    print (abstract)
                    #    assert False
                    yield abstract
                else:
                    if not 'noabstract' in stats:
                        stats['noabstract'] = 0
                    stats['noabstract'] += 1

def gen_hgvs(filename):
    hgvs_counter = 0
    
    for abstract in gen_abstracts(filename):
        
        transcripts = get_transcripts(abstract)
        
        for hgvs in gen_hgvs_2(abstract):
            hgvs_counter += 1

            if hgvs_counter % 100 == 0:
                print ('HGVS FOUND:', hgvs_counter)
            
            gene = get_gene_names(abstract, hgvs[1])
            
            yield abstract, gene, ''.join(hgvs), transcripts

def get_gene_names(abstract, hgvs):
    pos = abstract.index(hgvs)
    
    before = abstract[:pos]
    after = abstract[pos+len(hgvs):]
    
    #Check before
    before = before.split()[::-1]
    before = [noparenthesis(x) for x in before]
    
    for word in before:
        name = check_gene_name(word)
        if name:
            return name
    
    #Check after
    after = [noparenthesis(x) for x in after.split()]
    for word in after:
        name = check_gene_name(word)
        if name:
            return name
    
    if not 'no_gene' in stats:
        stats['no_gene'] = 0
        
    stats['no_gene'] += 1
    
    #print abstract
    #print hgvs
    
    #if stats['no_gene'] > 1:
    #    assert False
    return None

def gen_hgvs_2(abstract):
    #245 A>
    #found = re.findall(r'(.{1,100})([\d]+[\s]*[ACGT]+[\s]*>)(.{1,100})',abstract, re.UNICODE)
    found = re.findall(r'[\d]+[\s]*[ACGT]+[\s]*>',abstract, re.UNICODE)
    
    if not found:
        if not 'nohgvs' in stats:
            stats['nohgvs'] = 0
        stats['nohgvs'] += 1
    
    for f in found:
        start = abstract.index(f)
        before = abstract[:start]
        after = abstract[start+len(f):]
        
        # We do not want any HGVS before and after the one that we found
        before = before.replace('>','')
        after = after.replace('>', '')

        yield before, f, after
    

def get_transcripts(text):
    return re.findall(r'[A-Z][A-Z]_[\d]{4,15}\.?[\d]*', text, re.UNICODE)
        
def nowhite(p):
    return re.sub(r'[\s]', '', p, flags=re.UNICODE)

def noparenthesis(p):
    return re.sub(r'[\(\),\.\:]', '', p, flags=re.UNICODE)

def post_process(hgvs):

    s = None
    
    if not s:
        # c.6348+1G>A
        s = re.search(r'[CcGgpP][\s]*\.[\s]*[\d]+[\s]*[\+\-][\s]*[\d]+[\s]*[ACGT]+[\s]*>[\s]*[ACGT]+', hgvs, re.UNICODE)
    
    if not s:
        # c.969C > A
        s = re.search(r'[CcGgpPm][\s]*\.[\s]*[\d]+[\s]*[ACGT][\s]*>[\s]*[ACGTS]+', hgvs, re.UNICODE)
    
    if not s:
        # 236G > A
        s = re.search(r'[\d]+[\s]*[ACGT]+[\s]*>[\s]*[ACGT]+', hgvs, re.UNICODE)
    
    if not s:
        # c.743C > del 
        s = re.search(r'[cCgGpP]\.[\d]+[ACGT]+[\s]*>[\s]*del', hgvs, re.UNICODE)
    
    #print ('=====')
    if s:
        result = nowhite(s.group(0))
        #print (hgvs)
        #print (result)
        return result
    else:
        #print (hgvs)
        #assert False
        
        if not 'noparsehgvs' in stats:
            stats['noparsehgvs'] = 0
        stats['noparsehgvs'] += 1
        
        return None
        
        
def do_1():
    output_fn = 'parsed_abstracts.json'
    output_f = codecs.open(output_fn, 'w', 'utf-8')
    records = 0
    for abstract, gene, hgvs, transcripts in gen_hgvs('abstracts.json.gz'):
        hgvs = post_process(hgvs)
        if hgvs is None:
            continue

        
        records += 1
        if records % 100 == 0:
            print 'Records:', records
        
        #if records <8:
        #    continue
        
        #if records > 100:
        #    break
        
        to_save = {
            'abstract': abstract,
            'gene': gene,
            'hgvs': hgvs,
            'transcripts': transcripts,
            'record': records
        }
        
        #print gene, hgvs, transcripts
        if False:
            output_f.write('=========== {} ================\n'.format(records))
            output_f.write(abstract + '\n')
            output_f.write('GENE:' + gene + '\n')
            output_f.write('HGVS:'+ hgvs + '\n')
            output_f.write('Transcripts:' + str(transcripts) + '\n')
        if True:
            json.dump(to_save, output_f)
            output_f.write('\n')
            output_f.flush()
               
    output_f.close()
    print 'Generated:', output_fn
    
    with open('stats.json', 'w') as f:
        json.dump(stats, f)
    print 'Generated:', 'stats.json'

def do_2():
    counter={}
    for abstract in gen_abstracts('abstracts.json.gz', per=10000):
        for tr in ['NT_', 'NG_', 'NC_']:
            if tr in abstract:
                #print '=====  {}  ======'.format(tr)
                if not tr in counter:
                    counter[tr] = []
                    
                counter[tr].append(abstract)
                #print abstract
                #assert False
                
    #print (counter)
    return counter
        
do_1()
#do_2()









    



Overwriting run_1.py

RUN_2

Run with /home/user/mutationinfo/localpython/bin/python run_2.py



In [4]:

    
%%writefile run_2.py

#assert False # THIS IS ON PURPOSE. DO NOT RUN THIS

import re
import json
import subprocess

#import pandas as pd

from StringIO import StringIO

def execute(command):
    process = subprocess.Popen(command, shell=True,
                           stdout=subprocess.PIPE, 
                           stderr=subprocess.PIPE)

    # wait for the process to terminate
    out, err = process.communicate()
    errcode = process.returncode
    
    out = out.decode('utf-8')
    err = err.decode('utf-8')
    
    #print ('STDOUT:')
    #print (out)
    #print ('ERR:')
    #print (err)
    #print ('RETURN CODE:', errcode)
    
    return out

def inverse(s):
    
    return {
        'A': 'T',
        'T': 'A',
        'C': 'G',
        'G': 'C',
    }[s]

stats_2 = {}

def get_transvar_reference(coord, strand):
    s = re.search(r'chr[\dXY]+:g.[\d]+([ACGT]+)/', coord)
    if s:
        reference = s.group(1)
    else:
        return None

    if strand == '-':
        return inverse(reference)
    elif strand == '+':
        return reference
    else:
        assert False


def parse_transvar_output(output,command=None, hgvs=None, abstract=None):
    ls = output.split('\n')
    ls = [x.split('\t') for x in ls if x.strip()] 
    strand_i = ls[0].index('strand')
    coord_i = ls[0].index('coordinates(gDNA/cDNA/protein)')
    transcript_i = ls[0].index('transcript')
    
    ret = {l[transcript_i]:get_transvar_reference(l[coord_i], l[strand_i])  for l in ls[1:]}
    return ret    

def load_parsed_abstracts():
    with open('parsed_abstracts.json') as f:
        for l in f:
            data = json.loads(l)
            yield data
            
def apply_transvar():
    
    transvar_cmd_p = "/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i '{hgvs}' --refversion hg19"
    fn = 'parsed_abstracts_transvar.json'
    f = open(fn, 'w')
    counter = 0
    input_transvar_fn = 'genes_hgvs.txt'
    input_transvar_f = open(input_transvar_fn, 'w')
    for parsed in load_parsed_abstracts():
        counter += 1
        
        if counter < 0:
            continue
            
        #if counter > 100:
        #    break
        
        print 'Counter:', counter
        
        abstract = parsed['abstract']
        
        if 'dog' in abstract:
            stats_2['nothumnan'] = stats_2.get('nothumnan', 0) + 1
            continue

        
        #print parsed
        hgvs = parsed['hgvs']
        
        #Get hgvs reference
        s = re.search(r'([ACGT]+)>', hgvs)
        if not s:
            continue
            #assert False
            
        hgvs_reference = s.group(1)
                
        #If it starts with a number assuming coding position
        if re.search(r'^[\d]+', hgvs, re.UNICODE):
            hgvs = 'c.' + hgvs
            
            
        #Get everything except the reference
        s = re.search(r'^([^ACGT]+)[ACGT]+>', hgvs)
        if not s:
            continue
            #assert False
        except_reference = s.group(1)

        
        gene = parsed['gene']
        if not gene:
            continue
            #assert False

        transcripts = parsed['transcripts']
        if transcripts:
            pass
            #assert False
        
        hgvs = gene + ':' + hgvs
        hgvs_no_reference = gene + ':' + except_reference
        #transvar_cmd = transvar_cmd_p.format(hgvs=hgvs)
        transvar_cmd = transvar_cmd_p.format(hgvs=hgvs_no_reference)
        #print transvar_cmd
        #print abstract
        #transvar_output = execute(transvar_cmd) # DO NOT EXECUTE IT
        input_transvar_f.write('{}\t{}\n'.format(gene, except_reference))
        continue
        
        parsed['transvar'] = transvar_output
        f.write(json.dumps(parsed) + '\n')
        continue
        
        #print transvar_output
        #transvar_output_f = StringIO(transvar_output)
        #df = pd.read_csv(transvar_output_f, sep='\t')
        #print df
        
        transvar_references = parse_transvar_output(transvar_output, transvar_cmd, hgvs, abstract)
        if len(transvar_references) == 0:
            assert False
            
        if len(transvar_references) == 1:
            if transvar_references.values()[0] == hgvs_reference:
                stats_2['transvarok'] = stats_2.get('transvarok', 0) + 1
            else:                
                print transvar_cmd
                print 'HGVS:', hgvs
                print 'transvar_reference:', transvar_references.values()[0], 'Hgvs_reference:', hgvs_reference
                assert transvar_references.values()[0]
                assert hgvs_reference
                stats_2['1_reference_not_compatible'] = stats_2.get('1_reference_not_compatible', 0) + 1
        else:
            # Take all references
            all_references = list(set(transvar_references.values()))
            if len(all_references) == 1:
                if all_references[0] == hgvs_reference:
                    stats_2['1_reference_many_transcripts'] = stats_2.get('1_reference_many_transcripts', 0) + 1
                else:
                    assert False
            else:
                assert hgvs_reference # Not null
                assert [x for x in transvar_references.values() if x] # Not empty
                if hgvs_reference in all_references:
                    stats_2['many_references_exists'] = stats_2.get('many_references_exists', 0) + 1
                else:
                    stats_2['many_references_NOT_exists'] = stats_2.get('many_references_NOT_exists', 0) + 1

    f.close()
    input_transvar_f.close()
    print 'Created_file:', input_transvar_fn
    with open('stats_2.json', 'w') as f:
        json.dump(stats_2, f)
    
    print 'created file:', fn
    print 'Created file: stats_2.json'

def do_3():
    apply_transvar()
    
do_3()









    



Overwriting run_2.py

RUN:

/home/user/mutationinfo/localpython/bin/transvar canno --ccds -l genes_hgvs.txt -g 1 -m 2 --refversion hg19 --oneline > transvar_output.txt



In [10]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'RHAG:c.236G>A' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
RHAG:c.236G>A	CCDS4927 (protein_coding)	RHAG	-	chr6:g.49586997C>T/c.236G>A/p.S79N	inside_[cds_in_exon_2]	CSQN=Missense;reference_codon=AGT;alternative_codon=AAT;source=CCDS



In [26]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'EXT2:c.969C>A' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
EXT2:c.969C>A	.	.	.	././.	.	no_valid_transcript_found



In [44]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'EGFR:c.2576T>G' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
EGFR:c.2576T>G	.	.	.	././.	.	no_valid_transcript_found



In [50]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'EGFR:c.2576' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
EGFR:c.2576	CCDS5514 (protein_coding)	EGFR	+	chr7:g.55259518C/c.2576C/.	inside_[cds_in_exon_21]	source=CCDS

3 cases of exon 21 2576T>G mutation



In [54]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'EGFR:c.2576' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
EGFR:c.2576	CCDS5514 (protein_coding)	EGFR	+	chr7:g.55259518C/c.2576C/.	inside_[cds_in_exon_21]	source=CCDS



In [1]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'BRCA1:c.5251' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
BRCA1:c.5251	CCDS11453 (protein_coding)	BRCA1	-	chr17:g.41209095G/c.5251C/.	inside_[cds_in_exon_18]	source=CCDS
BRCA1:c.5251	CCDS11456 (protein_coding)	BRCA1	-	chr17:g.41215355T/c.5251A/.	inside_[cds_in_exon_18]	source=CCDS
BRCA1:c.5251	CCDS11459 (protein_coding)	BRCA1	-	chr17:g.41201152A/c.5251T/.	inside_[cds_in_exon_18]	source=CCDS



In [2]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'BRCA1:c.5251C>T' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
BRCA1:c.5251C>T	CCDS11453 (protein_coding)	BRCA1	-	chr17:g.41209095G>A/c.5251C>T/p.R1751*	inside_[cds_in_exon_18]	CSQN=Nonsense;reference_codon=CGA;alternative_codon=TGA;source=CCDS



In [67]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'BRCA1:c.5251A>T' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
BRCA1:c.5251A>T	CCDS11456 (protein_coding)	BRCA1	-	chr17:g.41215355T>A/c.5251A>T/p.N1751Y	inside_[cds_in_exon_18]	CSQN=Missense;reference_codon=AAT;alternative_codon=TAT;source=CCDS



In [6]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'IGSF1:c.2066' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
IGSF1:c.2066	CCDS14629 (protein_coding)	IGSF1	-	chrX:g.130412084G/c.2066C/.	inside_[cds_in_exon_12]	source=CCDS
IGSF1:c.2066	CCDS55490 (protein_coding)	IGSF1	-	chrX:g.130412057T/c.2066A/.	inside_[cds_in_exon_11]	source=CCDS
IGSF1:c.2066	CCDS55491 (protein_coding)	IGSF1	-	chrX:g.130412099G/c.2066C/.	inside_[cds_in_exon_12]	source=CCDS



In [10]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'IGSF1:c.2065+1G>A' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
IGSF1:c.2065+1G>A	.	.	.	././.	.	no_valid_transcript_found



In [11]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'FAH:c.1062+5' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
FAH:c.1062+5	CCDS10314 (protein_coding)	FAH	+	chr15:g.80472572G/c.1062+5G/.	inside_[intron_between_exon_12_and_13]	source=CCDS



In [17]:

    
!/home/user/mutationinfo/localpython/bin/transvar canno --ccds -i 'PCD:c.710' --refversion hg19









    



input	transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
[wrap_exception] warning: invalid_gene_PCD
PCD:c.710	.	.	.	././.	.	Error_invalid_gene_PCD

Run 3

Run with /home/user/mutationinfo/localpython/bin/python run_3.py



In [34]:

    
%%writefile run_3.py
import re
import json
import time
import requests

def load_parsed_abstracts():
    with open('parsed_abstracts.json') as f:
        for l in f:
            data = json.loads(l)
            yield data
            
def hgvs_from_record(parsed):
        
    abstract = parsed['abstract']

    if 'dog' in abstract:
        #stats_2['nothumnan'] = stats_2.get('nothumnan', 0) + 1
        return None


    #print parsed
    hgvs = parsed['hgvs']

    #Get hgvs reference
    s = re.search(r'([ACGT]+)>', hgvs)
    if not s:
        return None
        #assert False

    hgvs_reference = s.group(1)

    #If it starts with a number assuming coding position
    if re.search(r'^[\d]+', hgvs, re.UNICODE):
        hgvs = 'c.' + hgvs


    #Get everything except the reference
    s = re.search(r'^([^ACGT]+)[ACGT]+>', hgvs)
    if not s:
        return None
        #continue
        #assert False
    except_reference = s.group(1)


    gene = parsed['gene']
    if not gene:
        return None
        #assert False

    transcripts = parsed['transcripts']
    if transcripts:
        pass
        #assert False

    hgvs = gene + ':' + hgvs
    hgvs_no_reference = gene + ':' + except_reference
    #transvar_cmd = transvar_cmd_p.format(hgvs=hgvs)
    return hgvs

def vep_parse(hgvs):
    headers={ "Content-Type" : "application/json"}
    vep_url = "https://rest.ensembl.org/vep/human/hgvs/{var}?"

    url = vep_url.format(var=hgvs)
    responce = requests.get(url, headers=headers)
    if responce.ok:
        return responce.json()
    else:
        print ('Error:')
        print (responce.text)

def vep_parse_post(hgvs):

 
    server = "https://rest.ensembl.org"
    ext = "/vep/human/hgvs"
    headers={ "Content-Type" : "application/json", "Accept" : "application/json"}
    
    assert type(hgvs) is list
    #data = '[' + ','.join([rept(x) for x in hgvs]) + ']'
    data = json.dumps({"hgvs_notations": hgvs})
    print data
    
    r = requests.post(server+ext, headers=headers, data=data)
 
    if not r.ok:
        print ('ERROR:')
        print (r.text)
        return None
 
    decoded = r.json()
    return decoded

def vep_run():
    
    count = 0
    
    f = open('vep_results.json', 'w')
    
    all_hgvs = set()
    for parsed in load_parsed_abstracts():
        count += 1
        
        print ('count:', count)
        
        if count < 1:
            continue
            
        #if count > 10:
        #    break
        
        hgvs = hgvs_from_record(parsed)
        print hgvs
        
        if hgvs is None:
            continue
        
        all_hgvs.add(hgvs)
        if len(all_hgvs) <200:
            continue
        
        # Accessing VEP!
        vep = vep_parse_post(list(all_hgvs))
        
        # Saving
        f.write(json.dumps(vep) + '\n')
        
        #Emptying set
        all_hgvs = set()
        time.sleep(10) # Be nice
        
        #vep = vep_parse(hgvs)
        #vep = vep_parse_post([hgvs])
        #print vep
        #assert False

    # Last batch
    vep = vep_parse_post(list(all_hgvs))    
    f.write(json.dumps(vep) + '\n')

        
    f.close()
    print ('Created: vep_results.json')
        
vep_run()









    



Writing run_3.py



In [2]:

    
import hgvs.parser
import hgvs.dataproviders.uta









    



/home/user/mutationinfo/localpython/lib/python2.7/site-packages/psycopg2-2.7.4-py2.7-linux-x86_64.egg/psycopg2/__init__.py:144: UserWarning: The psycopg2 wheel package will be renamed from release 2.8; in order to keep installing from binary please use "pip install psycopg2-binary" instead. For details see: <http://initd.org/psycopg/docs/install.html#binary-install-from-pypi>.
  """)



In [3]:

    
hdp = hgvs.dataproviders.uta.connect()



In [4]:

    
hgvs_parser = hgvs.parser.Parser().parse_hgvs_variant



In [5]:

    
p = hgvs_parser('RHAG:c.236G>A')



In [17]:

    
import hgvs.variantmapper
import hgvs.assemblymapper



In [18]:

    
am = hgvs.assemblymapper.AssemblyMapper(hdp, alt_aln_method=u'genewise',)



In [19]:

    
am.c_to_g(p)









    



---------------------------------------------------------------------------
HGVSDataNotAvailableError                 Traceback (most recent call last)
<ipython-input-19-6f5829b3df9d> in <module>()
----> 1 am.c_to_g(p)

/home/user/mutationinfo/localpython/lib/python2.7/site-packages/hgvs-1.1.1-py2.7.egg/hgvs/assemblymapper.pyc in c_to_g(self, var_c)
     92 
     93     def c_to_g(self, var_c):
---> 94         alt_ac = self._alt_ac_for_tx_ac(var_c.ac)
     95         var_out = super(AssemblyMapper, self).c_to_g(var_c, alt_ac, alt_aln_method=self.alt_aln_method)
     96         return self._maybe_normalize(var_out)

/home/user/mutationinfo/localpython/lib/python2.7/site-packages/hgvs-1.1.1-py2.7.egg/hgvs/assemblymapper.pyc in _alt_ac_for_tx_ac(self, tx_ac)
    138         if len(alt_acs) == 0:
    139             raise HGVSDataNotAvailableError("No alignments for {tx_ac} in {an} using {am}".format(
--> 140                 tx_ac=tx_ac, an=self.assembly_name, am=self.alt_aln_method))
    141 
    142         if len(alt_acs) > 1:

HGVSDataNotAvailableError: No alignments for RHAG in GRCh38 using genewise



In [ ]:



In [12]:

    
variantmapper









    



---------------------------------------------------------------------------
NameError                                 Traceback (most recent call last)
<ipython-input-12-ce4f3ed11a66> in <module>()
----> 1 variantmapper

NameError: name 'variantmapper' is not defined

VEP but for hg19

Run with /home/user/mutationinfo/localpython/bin/python run_4.py



In [5]:

    
%%writefile run_4.py
import re
import json
import time
import requests

def load_parsed_abstracts():
    with open('parsed_abstracts.json') as f:
        for l in f:
            data = json.loads(l)
            yield data
            
def hgvs_from_record(parsed):
        
    abstract = parsed['abstract']

    if 'dog' in abstract:
        #stats_2['nothumnan'] = stats_2.get('nothumnan', 0) + 1
        return None


    #print parsed
    hgvs = parsed['hgvs']

    #Get hgvs reference
    s = re.search(r'([ACGT]+)>', hgvs)
    if not s:
        return None
        #assert False

    hgvs_reference = s.group(1)

    #If it starts with a number assuming coding position
    if re.search(r'^[\d]+', hgvs, re.UNICODE):
        hgvs = 'c.' + hgvs


    #Get everything except the reference
    s = re.search(r'^([^ACGT]+)[ACGT]+>', hgvs)
    if not s:
        return None
        #continue
        #assert False
    except_reference = s.group(1)


    gene = parsed['gene']
    if not gene:
        return None
        #assert False

    transcripts = parsed['transcripts']
    if transcripts:
        pass
        #assert False

    hgvs = gene + ':' + hgvs
    hgvs_no_reference = gene + ':' + except_reference
    #transvar_cmd = transvar_cmd_p.format(hgvs=hgvs)
    return hgvs

def vep_parse(hgvs):
    headers={ "Content-Type" : "application/json"}
    vep_url = "https://grch37.rest.ensembl.org/vep/human/hgvs/{var}?"

    url = vep_url.format(var=hgvs)
    responce = requests.get(url, headers=headers)
    if responce.ok:
        return responce.json()
    else:
        print ('Error:')
        print (responce.text)

def vep_parse_post(hgvs):

 
    server = "https://grch37.rest.ensembl.org"
    ext = "/vep/human/hgvs"
    headers={ "Content-Type" : "application/json", "Accept" : "application/json"}
    
    assert type(hgvs) is list
    #data = '[' + ','.join([rept(x) for x in hgvs]) + ']'
    data = json.dumps({"hgvs_notations": hgvs})
    print data
    
    r = requests.post(server+ext, headers=headers, data=data)
 
    if not r.ok:
        print ('ERROR:')
        print (r.text)
        return None
 
    decoded = r.json()
    return decoded

def vep_run():
    
    count = 0
    
    f = open('vep_results_hg19.json', 'w')
    
    all_hgvs = set()
    for parsed in load_parsed_abstracts():
        count += 1
        
        print ('count:', count)
        
        if count < 1:
            continue
            
        #if count > 10:
        #    break
        
        hgvs = hgvs_from_record(parsed)
        print hgvs
        
        if hgvs is None:
            continue
        
        all_hgvs.add(hgvs)
        if len(all_hgvs) <200:
            continue
        
        # Accessing VEP!
        vep = vep_parse_post(list(all_hgvs))
        
        #print vep
        #assert False
        
        # Saving
        f.write(json.dumps(vep) + '\n')
        f.flush()
        
        #Emptying set
        all_hgvs = set()
        time.sleep(10) # Be nice
        
        #vep = vep_parse(hgvs)
        #vep = vep_parse_post([hgvs])
        #print vep
        #assert False

    # Last batch
    vep = vep_parse_post(list(all_hgvs))    
    f.write(json.dumps(vep) + '\n')

        
    f.close()
    print ('Created: vep_results_hg19.json')
        
vep_run()









    



Overwriting run_4.py

Create stats



In [17]:

    
import json

def vep_info(vep):
    # Take only the essential info
    
    #print json.dumps(vep, indent=4)
    #transcripts = [x['transcript_id'] for x in vep['transcript_consequences']]
    transcripts = [x['gene_id'] for x in vep['transcript_consequences']]
    transcripts = set(transcripts)
    #print transcripts
    #assert False
    
    ret = {
        'chr': vep['seq_region_name'],
        'start' : vep['start'],
        'end' : vep['end'],
        'allele_string' : vep['allele_string'].split('/'),
        'strand' : vep['strand'],
        'tr': len(transcripts)
    }
   
    return ret

def load_vep_results(fn):    
    ret = {}
    
    with open(fn) as f:
        c = 0
        for l in f:
            c += 1
            data = json.loads(l)

            #print data[0]
            #assert False
            
            for variant in data:
                #if not 'BRCA1' in variant['id']:
                #    continue
                ret[variant['id']] = vep_info(variant)
            
    print 'Lines:', c
    print 'Record:', len(ret)
    return ret

#vep = load_vep_results('vep_results.json') # Replace this with 'vep_results_hg19.json'
vep = load_vep_results('vep_results_hg19.json') # Replace this with 'vep_results_hg19.json'









    



Lines: 158
Record: 15075



In [3]:

    
vep['RDH5:c.758T>G']









    Out[3]:





{'allele_string': [u'T', u'G'],
 'chr': u'12',
 'end': 56118130,
 'start': 56118130,
 'strand': 1}



In [ ]:



In [5]:

    
def load_transvar_results(fn):
    '''
    transvar_output.txt
    '''

    ret = {}
    with open(fn) as f:
        c=0
        for l in f:
            c+=1
            ls = l.replace('\n', '').split('\t')
            if c == 1:
                header = ls
                header_str = l
                continue
                
            ret[ls[0]] = '\t'.join(header[1:]) + '\n' + '\t'.join(ls[1:]).replace('|||\t', '\n')
            #break
        print ('Records:', c)
    return ret



In [6]:

    
transvar=load_transvar_results('transvar_output.txt')









    



('Records:', 42115)



In [4]:

    
transvar.keys()









    Out[4]:





['RHAG|c.236']



In [20]:

    
print transvar['PHKG2|c.553']









    



transcript	gene	strand	coordinates(gDNA/cDNA/protein)	region	info
CCDS10690 (protein_coding)	PHKG2	+	chr16:g.30764875C/c.553C/.	inside_[cds_in_exon_5]	source=CCDS	
CCDS54002 (protein_coding)	PHKG2	+	chr16:g.30764875C/c.553C/.	inside_[cds_in_exon_5]	source=CCDS



In [56]:

    
import re
import codecs
import json
import requests

def hgvs_from_record(parsed):
        
    abstract = parsed['abstract']

    if 'dog' in abstract:
        #stats_2['nothumnan'] = stats_2.get('nothumnan', 0) + 1
        return None


    #print parsed
    hgvs = parsed['hgvs']

    #Get hgvs reference
    s = re.search(r'([ACGT]+)>', hgvs)
    if not s:
        return None
        #assert False

    hgvs_reference = s.group(1)

    #If it starts with a number assuming coding position
    if re.search(r'^[\d]+', hgvs, re.UNICODE):
        hgvs = 'c.' + hgvs


    #Get everything except the reference
    s = re.search(r'^([^ACGT]+)[ACGT]+>', hgvs)
    if not s:
        return None
        #continue
        #assert False
    except_reference = s.group(1)


    gene = parsed['gene']
    if not gene:
        return None
        #assert False

    transcripts = parsed['transcripts']
    if transcripts:
        pass
        #assert False

    hgvs = gene + ':' + hgvs
    hgvs_no_reference = gene + ':' + except_reference
    transvar_key = gene + '|' + except_reference
    #transvar_cmd = transvar_cmd_p.format(hgvs=hgvs)
    return hgvs, hgvs_reference, transvar_key

def mutalyzer(var):
    r = requests.get('https://mutalyzer.nl/json/numberConversion' ,
    {
    'build' : 'hg19' ,
    'variant' : var,
    })
    print var
    
    if not r.ok:
        print r.text
        assert False
    
    data = r.json()
    if not data:
        print 'DATA RETURNED:', data
        print 'TEXT RETURNED:', r.text
        return None
    if not data[0]:
        print 'DATA RETURNED:', data
        print 'TEXT RETURNED:', r.text
        
        return None
    s = re.search(r'\.([\d]+)[ACGT]', data[0])
    if not s:
        print 'Could not parse:', r.text
        return None
    return int(s.group(1))
    #print ( data 
#OUTPUT : [ 'NC 000011 . 1 0 : g .112088901C>T' ]

def inverse(s):
    
    return {
        'A': 'T',
        'T': 'A',
        'C': 'G',
        'G': 'C',
    }[s]

def get_transvar_reference(coord, strand):
    s = re.search(r'chr[\dXY]+:g.[\d]+([ACGT]+)/', coord)
    if s:
        reference = s.group(1)
    else:
        return None

    if strand == '-':
        return inverse(reference)
    elif strand == '+':
        return reference
    else:
        assert False

def get_transvar_chromosome_position(coord):
    s = re.search(r'chr([\dXY]+):g.([\d]+)', coord)
    if s:
        return s.group(1), int(s.group(2))

    if coord == '././.':
        return None, None
    
    print 'coord:', coord
    raise Exception('Unknown coord')
        
    
    
def parse_transvar_output(output):
    ls = output.split('\n')
    ls = [x.split('\t') for x in ls if x.strip()]
    try:
        strand_i = ls[0].index('strand')
    except Exception as e:
        print '====='
        print output
        print '====='
        raise e
    coord_i = ls[0].index('coordinates(gDNA/cDNA/protein)')
    transcript_i = ls[0].index('transcript')
    
    try:
        ret = {l[transcript_i]:{
            'reference': get_transvar_reference(l[coord_i], l[strand_i]),
            'position': get_transvar_chromosome_position(l[coord_i]),
            } for l in ls[1:]}
    except Exception as e:
        print output
        raise e
    return ret    

def add_one(d, key):
    d[key] = d.get(key, 0) + 1

def load_transvar_results(fn):
    
    stats_3 = {}
    vep_tr_transcripts = []
    
    prob_ab_f = codecs.open('problematic_abstracts.json', 'w', 'utf-8')
    
    c = 0
    with open(fn) as f:
        for l in f:
            c += 1
            
            if c % 10000 == 0:
                print 'Records:', c
            
            data = json.loads(l)
            
            hgvs_from_record_ret = hgvs_from_record(data)
            if hgvs_from_record_ret is None:
                add_one(stats_3, 'COULD NOT FIND HGVS')
                
                if data['transcripts']:
                    add_one(stats_3, 'NT__ TRANSCRIPTS WITHOUT HGVS')
                
                continue
                                    
                
            hgvs, hgvs_reference, transvar_key = hgvs_from_record_ret
            #print hgvs
            #print hgvs_reference
            if transvar_key in transvar:
                transvar_output = transvar[transvar_key]
            else:
                transvar_output = ''
            
            
            #transvar_output = data['transvar'] # THERE IS NOT DATA THERE! FIX IT
            #print transvar_output
            if not transvar_output.strip():
                add_one(stats_3, 'transvar_crashed')
                transvar_info = None
            else:
                transvar_info = parse_transvar_output(transvar_output)
            #print transvar_info
            
            vep_info = vep.get(hgvs, None)
            #print vep_info
            
            ### TRANSVAR / VEP FOUND SOUMETHING
            NO_VEP = False
            YES_VEP = False
            NO_TR = False
            YES_TR = False
            
            if vep_info is None:
                NO_VEP = True
                add_one(stats_3, 'NO_VEP')
            else:
                YES_VEP = True
                add_one(stats_3, 'YES_VEP')
            
            if transvar_info and all([x['position'][1] is None for x in transvar_info.values()]):
                    #add_one(stats_3, 'transvar_found ././.')
                    # TODO: CHECK VEP HGVS_REF!!!
                    NO_TR = True
                    add_one(stats_3, 'NO_TR')
            else:
                YES_TR = True
                add_one(stats_3, 'YES_TR')
            
            assert NO_VEP != YES_VEP
            assert NO_TR != YES_TR
            
            for x in [('YES_VEP', YES_VEP), ('NO_VEP', NO_VEP)]:
                for y in [('YES_TR', YES_TR), ('NO_TR', NO_TR)]:
                    if x[1] and y[1]:
                        add_one(stats_3, x[0] + '_' + y[0])
            
            #continue
            
            #if YES_VEP and NO_TR:
            #    print data
            #    print '====='
            #    print vep_info
            #    #assert False
            
            #if NO_TR:
            #    continue
            
            # END OF TRANSVAR / VEP FOUND SOMETHING
            
            # CHECK tr_ <--> HGVS
            if data['transcripts']:
                add_one(stats_3, 'NT__ TRANSCRIPTS WITH HGVS')
                if any(['.' in x for x in data['transcripts']]):
                    add_one(stats_3, 'NT__ TRANSCRIPTS WITH HGVS AND VERSION')
                    
                if len(data['transcripts'])>1:
                    add_one(stats_3, 'NT__ TRANSCRIPTS MORE THAN ONE')
                else:
                    print hgvs
                    print hgvs_reference
                    print transvar_key
                    print data['transcripts']
                    tr_hgvs = data['transcripts'][0] + ':' + hgvs.split(':')[1]
                    print tr_hgvs
                    tr_position = mutalyzer(tr_hgvs)
                    print tr_position
                    #assert False
                    if not tr_position:
                        add_one(stats_3, 'MUTALYZER FAILED')
                    elif vep_info:
                        if vep_info['start'] == tr_position:
                            add_one(stats_3, 'MUTALYZER_OK')
                        else:
                            print vep_info
                            print data['abstract']
                            prob_ab_f.write(data['abstract'] + '\n')
                            add_one(stats_3, 'MUTALYZER MISMATCHED POSITION')
            #END OF tr_ <--> HGVS Check

            
            #### CHECK VEP // HGVS REFERENCE
            hgvs_vep_concordance = False
            if vep_info:
                if hgvs_reference in vep_info['allele_string']:
                    if vep_info['allele_string'].index(hgvs_reference) == 0:
                        add_one(stats_3, 'hgvs_reference_SAME_VEP')
                        hgvs_vep_concordance = True
                    else:
                        add_one(stats_3, 'hgvs_reference_NOT_SAME_VEP')
                else:
                    add_one(stats_3, 'hgvs_reference_NOT_PRESENT_IN_VEP')
            
            ### END OF VEP // HGVS REFERENCE CONCORDANC CHECK
            
            ### CHECK TRANSVAR CONCORDANCE
            if NO_TR:
                continue
            
            
            more_than_one = False
            reference_found = False
            reference_not_found = False
            more_than_one_marked = False
            vep_concordant = False
            vep_discordant = False
            transcript_counter = 0
            
            for k,v in transvar_info.iteritems():
                if more_than_one:
                    if not more_than_one_marked:
                        add_one(stats_3, 'more_than_one')
                        more_than_one_marked = True
                
                if v['reference'] == hgvs_reference:
                    reference_found = True
                    
                if v['reference'] != hgvs_reference:
                    reference_not_found = True
                
                if vep_info:
                    if v['reference'] in vep_info['allele_string']:
                        if vep_info['allele_string'].index(v['reference']) == 0:
                            if vep_info['start'] == v['position'][1]:
                                vep_concordant = True
                            else:
                                vep_discordant = True
                        else:
                            vep_discordant = True
                    else:
                        vep_discordant = True
                
                more_than_one = True
            
                transcript_counter += 1
            
            if not more_than_one:
                # Transvar found nada
                add_one(stats_3, 'transvar_not_found')
            else:
                add_one(stats_3, 'transvar_found_something')
            
            if reference_found:
                add_one(stats_3, 'reference_found')
            else:
                add_one(stats_3, 'reference_not_found')
                
            if reference_found and reference_not_found: # I know..
                add_one(stats_3, 'reference_found_and_reference_not_found')
                
            if reference_found and not reference_not_found:
                add_one(stats_3, 'reference_found_only')
                
            if not reference_found and reference_not_found:
                add_one(stats_3, 'not_reference_found_only')
                
            if not reference_found and not reference_not_found:
                assert False
            
            add_one(stats_3, 'TRANSCRIPT_COUNTER_{}'.format(transcript_counter))
            
            if vep_info:
                if vep_concordant:
                    add_one(stats_3, 'vep_concordant')

                if vep_discordant:
                    add_one(stats_3, 'vep_discordant')

                if vep_concordant and vep_discordant: # Can happen
                    add_one(stats_3, 'vep_concordant_and_discordant')

                if vep_concordant and not vep_discordant:
                    add_one(stats_3, 'vep_concordant_and_not_discordant')

                if not vep_concordant and vep_discordant:
                    add_one(stats_3, 'not_vep_concordant_and_discordant')

                if not vep_concordant and not vep_discordant:
                    add_one(stats_3, 'not_vep_concordant_not_discordant')

                vep_tr_transcripts.append((vep_info['tr'], transcript_counter))
                    
            if hgvs_vep_concordance and reference_found and not reference_not_found and vep_concordant and not vep_discordant:
                add_one(stats_3, 'ALL_PERFECT')
                
                if data['transcripts']:
                    add_one(stats_3, 'NT__ TRANSCRIPTS ALL PERFECT')
                    if any(['.' in x for x in data['transcripts']]):
                        add_one(stats_3, 'NT__ TRANSCRIPTS ALL PERFECT AND VERSION')
                    #print data['abstract']
                
                    
            
            #print (stats_3)
            #assert False
    prob_ab_f.close()
    print 'Created problematic_abstracts.json'
    print json.dumps(stats_3, indent=4)
    print 'Length of vep_tr_transcripts:', len(vep_tr_transcripts)
    
    return vep_tr_transcripts

#load_transvar_results('parsed_abstracts_transvar.json')
plot_data = load_transvar_results('parsed_abstracts.json')









    



FLNA:c.1621G>T
G
FLNA|c.1621
[u'NM_001456.3']
NM_001456.3:c.1621G>T
NM_001456.3:c.1621G>T
153593574
L2HGDH:c.178G>A
G
L2HGDH|c.178
[u'NM_024884.2']
NM_024884.2:c.178G>A
NM_024884.2:c.178G>A
50769698
AP4M1:c.991C>T
C
AP4M1|c.991
[u'NM_006594.4']
NM_006594.4:c.991C>T
NM_006594.4:c.991C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HSF4:c.190A>G
A
HSF4|c.190
[u'NM_001040667.2']
NM_001040667.2:c.190A>G
NM_001040667.2:c.190A>G
67199491
DMC1:c.106G>A
G
DMC1|c.106
[u'NM_007068.3']
NM_007068.3:c.106G>A
NM_007068.3:c.106G>A
38962732
WHRN:c.1814T>C
T
WHRN|c.1814
[u'NM_138691']
NM_138691:c.1814T>C
NM_138691:c.1814T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
NOG:c.611G>A
G
NOG|c.611
[u'NM_005450.4']
NM_005450.4:c.611G>A
NM_005450.4:c.611G>A
54672195
NR2F1:c.286A>G
A
NR2F1|c.286
[u'NM_005654']
NM_005654:c.286A>G
NM_005654:c.286A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
NBAS:c.3596G>A
G
NBAS|c.3596
[u'NM_015909.3']
NM_015909.3:c.3596G>A
NM_015909.3:c.3596G>A
15514839
NBAS:c.209+1G>A
G
NBAS|c.209+1
[u'NM_015909.3']
NM_015909.3:c.209+1G>A
NM_015909.3:c.209+1G>A
15696906
GNB1:c.230G>T
G
GNB1|c.230
[u'NM_001282539.1']
NM_001282539.1:c.230G>T
NM_001282539.1:c.230G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
FLCN:c.649C>T
C
FLCN|c.649
[u'NM_144997']
NM_144997:c.649C>T
NM_144997:c.649C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ETFDH:c.250G>A
G
ETFDH|c.250
[u'NM_004453']
NM_004453:c.250G>A
NM_004453:c.250G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ETFDH:c.920C>G
C
ETFDH|c.920
[u'NM_004453']
NM_004453:c.920C>G
NM_004453:c.920C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
EDNRB:c.1280C>T
C
EDNRB|c.1280
[u'NM_031857']
NM_031857:c.1280C>T
NM_031857:c.1280C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
EDNRB:c.1425C>G
C
EDNRB|c.1425
[u'NM_031857']
NM_031857:c.1425C>G
NM_031857:c.1425C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
IGF2:c.101G>A
G
IGF2|c.101
[u'NM_000612']
NM_000612:c.101G>A
NM_000612:c.101G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SMOC1:c.367T>C
T
SMOC1|c.367
[u'NM_001034852.2']
NM_001034852.2:c.367T>C
NM_001034852.2:c.367T>C
70420238
ZDHHC9:c.286C>T
C
ZDHHC9|c.286
[u'NM_001008222.2']
NM_001008222.2:c.286C>T
NM_001008222.2:c.286C>T
128962999
TMEM67:c.725A>G
A
TMEM67|c.725
[u'NM_153704.5']
NM_153704.5:c.725A>G
NM_153704.5:c.725A>G
94792831
ERCC8:c.1122G>C
G
ERCC8|c.1122
[u'NM_000082']
NM_000082:c.1122G>C
NM_000082:c.1122G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PAX6:c.1183+1G>A
G
PAX6|c.1183+1
[u'NG_008679.1']
NG_008679.1:c.1183+1G>A
NG_008679.1:c.1183+1G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
VARS2:c.3650G>A
G
VARS2|c.3650
[u'NM_006295']
NM_006295:c.3650G>A
NM_006295:c.3650G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
VARS2:c.3650G>A
G
VARS2|c.3650
[u'NM_006295']
NM_006295:c.3650G>A
NM_006295:c.3650G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
BBS2:c.1677C>A
C
BBS2|c.1677
[u'NM_024685.3']
NM_024685.3:c.1677C>A
NM_024685.3:c.1677C>A
76740088
BBS2:c.1974T>G
T
BBS2|c.1974
[u'NM_024685.3']
NM_024685.3:c.1974T>G
NM_024685.3:c.1974T>G
76739791
{'end': 56519587, 'tr': 1, 'allele_string': [u'T', u'G'], 'start': 56519587, 'chr': u'16', 'strand': -1}
We report a 10-year-old girl with Bardet-Biedl syndrome caused by a novel mutation in the Bardet-Biedl syndrome 10 (BBS10) gene. She had multiple malformations, including a dysmorphic face, postaxial polydactyly, polycystic kidney and amblyopia. She presented with typical BBS features, including intellectual disability with emotional outbursts and mild obesity. Whole-exome sequencing identified compound heterozygous mutations with NM_024685.3:c.1677C>A [p.(Tyr559*)] and c.1974T>G [p.(Tyr658*)]. To our knowledge, the latter mutation has never been reported previously.
KCNQ2:c.601C>T
C
KCNQ2|c.601
[u'NM_172107.2']
NM_172107.2:c.601C>T
NM_172107.2:c.601C>T
62076101
MAT1A:c.1081G>T
G
MAT1A|c.1081
[u'NM_000429.2']
NM_000429.2:c.1081G>T
NM_000429.2:c.1081G>T
82034280
CD151:c.351+2T>C
T
CD151|c.351+2
[u'NM_139029']
NM_139029:c.351+2T>C
NM_139029:c.351+2T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
AR:c.2450-42G>A
G
AR|c.2450-42
[u'NM_000044.4']
NM_000044.4:c.2450-42G>A
NM_000044.4:c.2450-42G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
B3GAT3:c.667G>A
G
B3GAT3|c.667
[u'NM_012200']
NM_012200:c.667G>A
NM_012200:c.667G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
COQ8B:c.521A>G
A
COQ8B|c.521
[u'NM_024876.3']
NM_024876.3:c.521A>G
NM_024876.3:c.521A>G
41211056
NADK2:g.36241900A>G
A
NADK2|g.36241900
[u'NM_001085411.1']
NM_001085411.1:g.36241900A>G
NM_001085411.1:g.36241900A>G
DATA RETURNED: None
TEXT RETURNED: null
None
ZZZ3:c.122G>T
G
ZZZ3|c.122
[u'NM_170707.3']
NM_170707.3:c.122G>T
NM_170707.3:c.122G>T
156084831
PEX10:c.530T>G
T
PEX10|c.530
[u'NM_153818.1']
NM_153818.1:c.530T>G
NM_153818.1:c.530T>G
2339961
FBXO7:c.1408G>T
G
FBXO7|c.1408
[u'NM_012179.3']
NM_012179.3:c.1408G>T
NM_012179.3:c.1408G>T
32894356
FBXO7:c.152A>G
A
FBXO7|c.152
[u'NM_012179.3']
NM_012179.3:c.152A>G
NM_012179.3:c.152A>G
32874997
PRF1:c.1120T>G
T
PRF1|c.1120
[u'NM_001083116']
NM_001083116:c.1120T>G
NM_001083116:c.1120T>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PAH:c.2A>G
A
PAH|c.2
[u'NM_001456']
NM_001456:c.2A>G
NM_001456:c.2A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PAH:c.2A>G
A
PAH|c.2
[u'NM_001456']
NM_001456:c.2A>G
NM_001456:c.2A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
STAG3:c.1573+5G>A
G
STAG3|c.1573+5
[u'NM_012447.2']
NM_012447.2:c.1573+5G>A
NM_012447.2:c.1573+5G>A
99796995
FH:c.1G>C
G
FH|c.1
[u'NM_000143.3']
NM_000143.3:c.1G>C
NM_000143.3:c.1G>C
241683022
FH:c.1G>C
G
FH|c.1
[u'NM_000143.3']
NM_000143.3:c.1G>C
NM_000143.3:c.1G>C
241683022
MRE11:c.1090C>T
C
MRE11|c.1090
[u'NM_005590']
NM_005590:c.1090C>T
NM_005590:c.1090C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC12A3:c.1276A>T
A
SLC12A3|c.1276
[u'NM_000339.2']
NM_000339.2:c.1276A>T
NM_000339.2:c.1276A>T
56913080
PRKD1:c.979G>A
G
PRKD1|c.979
[u'NM_000744']
NM_000744:c.979G>A
NM_000744:c.979G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PITX2:c.272G>A
G
PITX2|c.272
[u'NM_153427.2']
NM_153427.2:c.272G>A
NM_153427.2:c.272G>A
111539825
{'end': 111542459, 'tr': 1, 'allele_string': [u'G', u'A'], 'start': 111542459, 'chr': u'4', 'strand': -1}
Axenfeld-Rieger syndrome is a rare autosomal dominant condition. Anomalies include anterior segment dysgenesis of the eye, dental anomalies, maxillary hypoplasia, periumbilical anomalies, and congenital heart defects. We report a patient with Peters anomaly, dysmorphic features, congenital heart defect, umbilical hernia, short stature, and developmental delay. Diagnostic sequencing of 23 genes known to be causally related to the condition was performed on the patient, parents, and maternal grandparents. A variant of uncertain significance in PITX2 was identified. The mother had the same mutation and the father did not. The mother had decreased vision, congenitally missing teeth, and required jaw surgery as a child. Her asymptomatic parents elected to be tested and were negative for the mutation. The mutation, NM_153427.2:c.272G>A (p.Arg91Gln), is predicted to be damaging by PolyPhen-2 (score of 0.997), identified as a missense mutation with an allele frequency of 1.648e-05 by the Exome Aggregation Consortium, and has been reported in ClinVar once, by the laboratory that analyzed our patient's sample. Due to the in silico predictions and the results of family studies, it is suggested that this variant can be classified as pathogenic according to the American College of Medical Genetics and Genomics 2015 rule Pathogenic(iii)(b), specifically rules PS2, PM2, PM5, PP1, and PP3.
CAMTA2:c.6G>A
G
CAMTA2|c.6
[u'NM_001171166.1']
NM_001171166.1:c.6G>A
NM_001171166.1:c.6G>A
4890919
FBP1:c.825+1G>A
G
FBP1|c.825+1
[u'NM_000507.3']
NM_000507.3:c.825+1G>A
NM_000507.3:c.825+1G>A
97367738
FBP1:c.355G>A
G
FBP1|c.355
[u'NM_000507.3']
NM_000507.3:c.355G>A
NM_000507.3:c.355G>A
97380121
FBP1:c.490G>A
G
FBP1|c.490
[u'NM_000507.3']
NM_000507.3:c.490G>A
NM_000507.3:c.490G>A
97372280
POLD1:c.3209T>A
T
POLD1|c.3209
[u'NM_002691.3']
NM_002691.3:c.3209T>A
NM_002691.3:c.3209T>A
50920517
HP:c.190+1G>C
G
HP|c.190+1
[u'NM_001126102.1']
NM_001126102.1:c.190+1G>C
NM_001126102.1:c.190+1G>C
72090531
NEDD4L:c.2617G>A
G
NEDD4L|c.2617
[u'NM_015277']
NM_015277:c.2617G>A
NM_015277:c.2617G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
TGFBR2:c.1381T>C
T
TGFBR2|c.1381
[u'NM_003242.5']
NM_003242.5:c.1381T>C
NM_003242.5:c.1381T>C
30715723
{'end': 30715648, 'tr': 1, 'allele_string': [u'T', u'C'], 'start': 30715648, 'chr': u'3', 'strand': 1}
Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized mainly by cardiovascular, craniofacial and skeletal features. We report on a patient with LDS, whose prenatal examination was compatible with the diagnosis of arthrogryposis multiplex congenita. Neonatal assessment showed craniofacial and cardiovascular findings suggestive of LDS whose diagnosis was confirmed by the detection of a novel mutation (HGVN: NM_003242.5 (TGFBR2): c.1381T > C (p.(Cys461Arg))) in the TGFBR2 gene. Few prenatal and neonatal cases of LDS have been reported in the literature. We reviewed all cases reported to date with perinatal onset to delineate the clinical manifestations that allow us to prompt diagnosis of this syndrome at an early stage to prevent fatal cardiovascular complications. Furthermore we discuss the multidisciplinary follow up required in these patients.
ATRX:c.7156C>T
C
ATRX|c.7156
[u'NM_000489.4']
NM_000489.4:c.7156C>T
NM_000489.4:c.7156C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
FAP:c.325G>C
G
FAP|c.325
[u'NM_000371.3']
NM_000371.3:c.325G>C
NM_000371.3:c.325G>C
29175207
FAP:c.325G>C
G
FAP|c.325
[u'NM_000371.3']
NM_000371.3:c.325G>C
NM_000371.3:c.325G>C
29175207
DHX15:c.664C>G
C
DHX15|c.664
[u'NM_001358']
NM_001358:c.664C>G
NM_001358:c.664C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ALDH18A1:c.377G>A
G
ALDH18A1|c.377
[u'NM_002860.3']
NM_002860.3:c.377G>A
NM_002860.3:c.377G>A
97397120
EMC1:c.19564510C>T
C
EMC1|c.19564510
[u'NM_015047.2']
NM_015047.2:c.19564510C>T
NM_015047.2:c.19564510C>T
Could not parse: ["NC_000001.10:g.-15731G>A"]
None
EMC1:c.1212+1G>A
G
EMC1|c.1212+1
[u'NM_015047.2']
NM_015047.2:c.1212+1G>A
NM_015047.2:c.1212+1G>A
19564510
POFUT1:c.485C>T
C
POFUT1|c.485
[u'NM_015352.1']
NM_015352.1:c.485C>T
NM_015352.1:c.485C>T
30804467
FGFR1:c.1115G>A
G
FGFR1|c.1115
[u'NM_001174067']
NM_001174067:c.1115G>A
NM_001174067:c.1115G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PSEN1:c.1164C>G
C
PSEN1|c.1164
[u'NM_000021.3']
NM_000021.3:c.1164C>G
NM_000021.3:c.1164C>G
73683868
COL4A5:c.2245-40A>G
A
COL4A5|c.2245-40
[u'NM_000091.4']
NM_000091.4:c.2245-40A>G
NM_000091.4:c.2245-40A>G
228145137
{'end': 107849932, 'tr': 1, 'allele_string': [u'A', u'G'], 'start': 107849932, 'chr': u'X', 'strand': 1}
Alport syndrome (AS) is an inherited progressive renal disease caused by mutations in COL4A3, COL4A4, and COL4A5 genes. Despite simultaneous screening of these genes being widely available, mutation detection still remains incomplete in a non-marginal portion of patients. Here, we applied whole-exome sequencing (WES) in 3 Italian families negative after candidate-gene analyses. In Family 1, we identified a novel heterozygous intronic variant (c.2245-40A>G) -outside the conventionally screened candidate region for diagnosis- potentially disrupting COL4A5 exon29 splicing. Using a minigene-based approach in HEK293 cells we demonstrated that this variant abolishes exon29 branch site, causing exon skipping. Moreover, skewed X-inactivation of the c.2245-40A>G allele correlated with disease severity in heterozygous females. In Family 2, WES highlighted a novel COL4A5 hemizygous missense mutation (p.Gly491Asp), which segregates with the phenotype and impacts on a highly-conserved residue. Finally, in Family 3, we detected a homozygous 24-bp in-frame deletion in COL4A3 exon1 (NM_000091.4:c.30_53del:p.Val11_Leu18del or c.40_63del24:p.Leu14_Leu21del), which is ambiguously annotated in databases, although it corresponds to a recurrent AS mutation. Functional analyses showed that this deletion disrupts COL4A3 signal peptide, possibly altering protein secretion. In conclusion, WES -together with functional studies- was fundamental for molecular diagnosis in 3 AS families, highlighting pathogenic variants that escaped previous screenings.
COL4A5:c.2245-40A>G
A
COL4A5|c.2245-40
[u'NM_000091.4']
NM_000091.4:c.2245-40A>G
NM_000091.4:c.2245-40A>G
228145137
{'end': 107849932, 'tr': 1, 'allele_string': [u'A', u'G'], 'start': 107849932, 'chr': u'X', 'strand': 1}
Alport syndrome (AS) is an inherited progressive renal disease caused by mutations in COL4A3, COL4A4, and COL4A5 genes. Despite simultaneous screening of these genes being widely available, mutation detection still remains incomplete in a non-marginal portion of patients. Here, we applied whole-exome sequencing (WES) in 3 Italian families negative after candidate-gene analyses. In Family 1, we identified a novel heterozygous intronic variant (c.2245-40A>G) -outside the conventionally screened candidate region for diagnosis- potentially disrupting COL4A5 exon29 splicing. Using a minigene-based approach in HEK293 cells we demonstrated that this variant abolishes exon29 branch site, causing exon skipping. Moreover, skewed X-inactivation of the c.2245-40A>G allele correlated with disease severity in heterozygous females. In Family 2, WES highlighted a novel COL4A5 hemizygous missense mutation (p.Gly491Asp), which segregates with the phenotype and impacts on a highly-conserved residue. Finally, in Family 3, we detected a homozygous 24-bp in-frame deletion in COL4A3 exon1 (NM_000091.4:c.30_53del:p.Val11_Leu18del or c.40_63del24:p.Leu14_Leu21del), which is ambiguously annotated in databases, although it corresponds to a recurrent AS mutation. Functional analyses showed that this deletion disrupts COL4A3 signal peptide, possibly altering protein secretion. In conclusion, WES -together with functional studies- was fundamental for molecular diagnosis in 3 AS families, highlighting pathogenic variants that escaped previous screenings.
NR3C2:c.1781G>A
G
NR3C2|c.1781
[u'NM_021625.4']
NM_021625.4:c.1781G>A
NM_021625.4:c.1781G>A
110230500
CYREN:c.481C>T
C
CYREN|c.481
[u'NM_000551.3']
NM_000551.3:c.481C>T
NM_000551.3:c.481C>T
10191488
ALG9:c.860A>G
A
ALG9|c.860
[u'NM_1234567890']
NM_1234567890:c.860A>G
NM_1234567890:c.860A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
JAG1:c.205C>T
C
JAG1|c.205
[u'NM_032193.3']
NM_032193.3:c.205C>T
NM_032193.3:c.205C>T
65487856
DNMT3A:c.2323-2A>T
A
DNMT3A|c.2323-2
[u'NM_022552.4']
NM_022552.4:c.2323-2A>T
NM_022552.4:c.2323-2A>T
25462086
AARS2:c.578T>G
T
AARS2|c.578
[u'NM_020745.3']
NM_020745.3:c.578T>G
NM_020745.3:c.578T>G
44279130
AARS2:c.595C>T
C
AARS2|c.595
[u'NM_020745.3']
NM_020745.3:c.595C>T
NM_020745.3:c.595C>T
44278885
CUL4B:c.2698G>T
G
CUL4B|c.2698
[u'NM_003588.3']
NM_003588.3:c.2698G>T
NM_003588.3:c.2698G>T
119660660
OCLN:c.1037+5G>C
G
OCLN|c.1037+5
[u'NM_001205254']
NM_001205254:c.1037+5G>C
NM_001205254:c.1037+5G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
OCLN:c.1169C>G
C
OCLN|c.1169
[u'NM_001205254']
NM_001205254:c.1169C>G
NM_001205254:c.1169C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PGAP3:c.851A>G
A
PGAP3|c.851
[u'NM_033419.3']
NM_033419.3:c.851A>G
NM_033419.3:c.851A>G
37829352
KAT6B:c.4943C>G
C
KAT6B|c.4943
[u'NM_001256468.1']
NM_001256468.1:c.4943C>G
NM_001256468.1:c.4943C>G
76790074
{'end': 76789525, 'tr': 2, 'allele_string': [u'C', u'G'], 'start': 76789525, 'chr': u'10', 'strand': 1}
Say-Barber/Biesecker/Young-Simpson syndrome (SBBYSS; OMIM 603736) is a rare syndrome with multiple congenital anomalies/malformations. The clinical diagnosis is usually based on a phenotype with a mask-like face and severe blepharophimosis and ptosis as well as other distinctive facial traits. We present a girl with dysmorphic features, an atrial septal defect, and developmental delay. Previous genetic testing (array-CGH, 22q11 deletion, PTPN11 and MLL2 mutation analysis) gave normal results. We performed whole-exome sequencing (WES) and identified a heterozygous nonsense mutation in the KAT6B gene, NM_001256468.1: c.4943C>G (p.S1648*). The mutation led to a premature stop codon and occurred de novo. KAT6B sequence variants have previously been identified in patients with SBBYSS, and the phenotype of the girl is similar to other patients diagnosed with SBBYSS. This case report provides additional evidence for the correlation between the KAT6B mutation and SBBYSS. If a patient is suspected of having a blepharophimosis syndrome or SBBYSS, we recommend sequencing the KAT6B gene. This is a further example showing that WES can assist diagnosis.
GNB4:c.169A>G
A
GNB4|c.169
[u'NM_021629.3']
NM_021629.3:c.169A>G
NM_021629.3:c.169A>G
179137221
COL5A2:c.682G>A
G
COL5A2|c.682
[u'NM_000393.3']
NM_000393.3:c.682G>A
NM_000393.3:c.682G>A
189951460
TRAPPC11:c.1893+3A>G
A
TRAPPC11|c.1893+3
[u'NM_021942.5']
NM_021942.5:c.1893+3A>G
NM_021942.5:c.1893+3A>G
184607904
TRAPPC11:c.904A>G
A
TRAPPC11|c.904
[u'NM_021942.5']
NM_021942.5:c.904A>G
NM_021942.5:c.904A>G
184600578
PIEZO2:c.1384C>T
C
PIEZO2|c.1384
[u'NM_022068']
NM_022068:c.1384C>T
NM_022068:c.1384C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
KRT3:c.174C>T
C
KRT3|c.174
[u'NM_000280']
NM_000280:c.174C>T
NM_000280:c.174C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.4567A>G
A
SLC26A4|c.4567
[u'NM_022124']
NM_022124:c.4567A>G
NM_022124:c.4567A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.5101G>A
G
SLC26A4|c.5101
[u'NM_022124']
NM_022124:c.5101G>A
NM_022124:c.5101G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.4567A>G
A
SLC26A4|c.4567
[u'NM_022124']
NM_022124:c.4567A>G
NM_022124:c.4567A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.5101G>A
G
SLC26A4|c.5101
[u'NM_022124']
NM_022124:c.5101G>A
NM_022124:c.5101G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.4567A>G
A
SLC26A4|c.4567
[u'NM_022124']
NM_022124:c.4567A>G
NM_022124:c.4567A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.5101G>A
G
SLC26A4|c.5101
[u'NM_022124']
NM_022124:c.5101G>A
NM_022124:c.5101G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ZZZ3:c.323C>T
C
ZZZ3|c.323
[u'NM_004614.4']
NM_004614.4:c.323C>T
NM_004614.4:c.323C>T
66565335
IDS:c.85C>T
C
IDS|c.85
[u'NM_000202.7']
NM_000202.7:c.85C>T
NM_000202.7:c.85C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PSMB8:c.212C>T
C
PSMB8|c.212
[u'NM_004159.4']
NM_004159.4:c.212C>T
NM_004159.4:c.212C>T
32810790
IDS:c.85C>T
C
IDS|c.85
[u'NM_000202.7']
NM_000202.7:c.85C>T
NM_000202.7:c.85C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
IDS:c.182C>T
C
IDS|c.182
[u'NM_000202.7']
NM_000202.7:c.182C>T
NM_000202.7:c.182C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CTU2:c.873G>A
G
CTU2|c.873
[u'NM_001012762.1']
NM_001012762.1:c.873G>A
NM_001012762.1:c.873G>A
88779855
DIAPH1:c.3637C>T
C
DIAPH1|c.3637
[u'NM_005219']
NM_005219:c.3637C>T
NM_005219:c.3637C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MEFV:c.2082G>A
G
MEFV|c.2082
[u'NM_000243.2']
NM_000243.2:c.2082G>A
NM_000243.2:c.2082G>A
3293405
AHSG:c.950G>A
G
AHSG|c.950
[u'NM_001622']
NM_001622:c.950G>A
NM_001622:c.950G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HSPE1:c.217C>T
C
HSPE1|c.217
[u'NM_002157.2']
NM_002157.2:c.217C>T
NM_002157.2:c.217C>T
198367811
MTO1:c.1510C>T
C
MTO1|c.1510
[u'NM_001123226']
NM_001123226:c.1510C>T
NM_001123226:c.1510C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MTO1:c.1669G>A
G
MTO1|c.1669
[u'NM_001123226']
NM_001123226:c.1669G>A
NM_001123226:c.1669G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ZZZ3:c.484T>C
T
ZZZ3|c.484
[u'NM_006941.3']
NM_006941.3:c.484T>C
NM_006941.3:c.484T>C
38374087
SOX10:c.163A>T
A
SOX10|c.163
[u'NM_006941.3']
NM_006941.3:c.163A>T
NM_006941.3:c.163A>T
38379629
GC:c.2494G>A
G
GC|c.2494
[u'NM_004360.4']
NM_004360.4:c.2494G>A
NM_004360.4:c.2494G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
BSCL2:c.985C>T
C
BSCL2|c.985
[u'NM_001122955.3']
NM_001122955.3:c.985C>T
NM_001122955.3:c.985C>T
62458772
NARFL:c.482G>T
G
NARFL|c.482
[u'NM_022493']
NM_022493:c.482G>T
NM_022493:c.482G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
RNF216:c.2061G>A
G
RNF216|c.2061
[u'NM_207111.3']
NM_207111.3:c.2061G>A
NM_207111.3:c.2061G>A
5751392
TNNT3:c.1956150G>A
G
TNNT3|c.1956150
[u'NM_006757.3']
NM_006757.3:c.1956150G>A
NM_006757.3:c.1956150G>A
3915095
TNNT3:c.681+1G>A
G
TNNT3|c.681+1
[u'NM_006757.3']
NM_006757.3:c.681+1G>A
NM_006757.3:c.681+1G>A
1956150
SLC26A4:c.2118C>A
C
SLC26A4|c.2118
[u'NP_000432.1']
NP_000432.1:c.2118C>A
NP_000432.1:c.2118C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.919-2A>G
A
SLC26A4|c.919-2
[u'NP_000432.1']
NP_000432.1:c.919-2A>G
NP_000432.1:c.919-2A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.919-2A>G
A
SLC26A4|c.919-2
[u'NP_000432.1']
NP_000432.1:c.919-2A>G
NP_000432.1:c.919-2A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.2118C>A
C
SLC26A4|c.2118
[u'NP_000432.1']
NP_000432.1:c.2118C>A
NP_000432.1:c.2118C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.2118C>A
C
SLC26A4|c.2118
[u'NP_000432.1']
NP_000432.1:c.2118C>A
NP_000432.1:c.2118C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.2118C>A
C
SLC26A4|c.2118
[u'NP_000432.1']
NP_000432.1:c.2118C>A
NP_000432.1:c.2118C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.2118C>A
C
SLC26A4|c.2118
[u'NP_000432.1']
NP_000432.1:c.2118C>A
NP_000432.1:c.2118C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.2118C>A
C
SLC26A4|c.2118
[u'NP_000432.1']
NP_000432.1:c.2118C>A
NP_000432.1:c.2118C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SLC26A4:c.919-2A>G
A
SLC26A4|c.919-2
[u'NP_000432.1']
NP_000432.1:c.919-2A>G
NP_000432.1:c.919-2A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ABCA3:c.604G>A
G
ABCA3|c.604
[u'NM_001089']
NM_001089:c.604G>A
NM_001089:c.604G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
WDR45:c.830+2T>C
T
WDR45|c.830+2
[u'NM_007075.3']
NM_007075.3:c.830+2T>C
NM_007075.3:c.830+2T>C
48933021
TTN:c.88880A>C
A
TTN|c.88880
[u'NM_001256850.1']
NM_001256850.1:c.88880A>C
NM_001256850.1:c.88880A>C
179412550
FOXF1:c.86544406C>A
C
FOXF1|c.86544406
[u'NM_001451']
NM_001451:c.86544406C>A
NM_001451:c.86544406C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
IL33:c.487-1G>C
G
IL33|c.487-1
[u'NM_001199640']
NM_001199640:c.487-1G>C
NM_001199640:c.487-1G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
TCTN1:c.342-2A>G
A
TCTN1|c.342-2
[u'NM_001082538.2']
NM_001082538.2:c.342-2A>G
NM_001082538.2:c.342-2A>G
111064165
COL1A2:c.2123G>A
G
COL1A2|c.2123
[u'NM_000089.3']
NM_000089.3:c.2123G>A
NM_000089.3:c.2123G>A
94049588
MEGF10:c.2981-2A>G
A
MEGF10|c.2981-2
[u'NM_032446.2']
NM_032446.2:c.2981-2A>G
NM_032446.2:c.2981-2A>G
126790256
HYLS1:c.900A>C
A
HYLS1|c.900
[u'NM_145014.2']
NM_145014.2:c.900A>C
NM_145014.2:c.900A>C
125770163
CPS1:c.603G>C
G
CPS1|c.603
[u'NM_153006.2']
NM_153006.2:c.603G>C
NM_153006.2:c.603G>C
42083181
CPS1:c.603G>C
G
CPS1|c.603
[u'NM_153006.2']
NM_153006.2:c.603G>C
NM_153006.2:c.603G>C
42083181
ATP8A2:c.1287G>T
G
ATP8A2|c.1287
[u'NM_016529']
NM_016529:c.1287G>T
NM_016529:c.1287G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ATP8A2:c.1630G>C
G
ATP8A2|c.1630
[u'NM_016529']
NM_016529:c.1630G>C
NM_016529:c.1630G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ATP8A2:c.1873C>T
C
ATP8A2|c.1873
[u'NM_016529']
NM_016529:c.1873C>T
NM_016529:c.1873C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ATP8A2:c.1128C>G
C
ATP8A2|c.1128
[u'NM_016529']
NM_016529:c.1128C>G
NM_016529:c.1128C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MSX1:c.4861985T>G
T
MSX1|c.4861985
[u'NM_002448']
NM_002448:c.4861985T>G
NM_002448:c.4861985T>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MSX1:c.359T>G
T
MSX1|c.359
[u'NM_002448']
NM_002448:c.359T>G
NM_002448:c.359T>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
RARS:c.5A>G
A
RARS|c.5
[u'NM_002887.3']
NM_002887.3:c.5A>G
NM_002887.3:c.5A>G
167913508
RARS:c.1367C>T
C
RARS|c.1367
[u'NM_002887.3']
NM_002887.3:c.1367C>T
NM_002887.3:c.1367C>T
167937606
SCN5A:c.5284G>T
G
SCN5A|c.5284
[u'NM_000335']
NM_000335:c.5284G>T
NM_000335:c.5284G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
BAZ1A:c.4043T>G
T
BAZ1A|c.4043
[u'NM_182648.2']
NM_182648.2:c.4043T>G
NM_182648.2:c.4043T>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PTEN:c.138C>A
C
PTEN|c.138
[u'NM_000314']
NM_000314:c.138C>A
NM_000314:c.138C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MTHFR:c.1530A>G
A
MTHFR|c.1530
[u'NM_005957.4']
NM_005957.4:c.1530A>G
NM_005957.4:c.1530A>G
11853964
ZZZ3:c.1129C>T
C
ZZZ3|c.1129
[u'NM_005957.4']
NM_005957.4:c.1129C>T
NM_005957.4:c.1129C>T
11854823
BBS2:c.4428+3A>G
A
BBS2|c.4428+3
[u'NM_015662.2']
NM_015662.2:c.4428+3A>G
NM_015662.2:c.4428+3A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PIK3R1:c.1425+1G>A
G
PIK3R1|c.1425+1
[u'NM_181523.2']
NM_181523.2:c.1425+1G>A
NM_181523.2:c.1425+1G>A
67589663
TP63:c.1063G>C
G
TP63|c.1063
[u'NM_003722.4']
NM_003722.4:c.1063G>C
NM_003722.4:c.1063G>C
189586439
GNB4:c.659T>C
T
GNB4|c.659
[u'NM_021629.3']
NM_021629.3:c.659T>C
NM_021629.3:c.659T>C
179131240
COL11A1:c.3168+5G>A
G
COL11A1|c.3168+5
[u'NM_001854.3']
NM_001854.3:c.3168+5G>A
NM_001854.3:c.3168+5G>A
103427417
KIF1A:c.2909G>A
G
KIF1A|c.2909
[u'NM_001244008.1']
NM_001244008.1:c.2909G>A
NM_001244008.1:c.2909G>A
241689914
GPI:c.1640G>A
G
GPI|c.1640
[u'NM_001127178.1']
NM_001127178.1:c.1640G>A
NM_001127178.1:c.1640G>A
517273
KNL1:c.6673-19T>A
T
KNL1|c.6673-19
[u'NM_170589.4']
NM_170589.4:c.6673-19T>A
NM_170589.4:c.6673-19T>A
40949534
C1QA:c.622C>T
C
C1QA|c.622
[u'NM_015991']
NM_015991:c.622C>T
NM_015991:c.622C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
C1QA:c.164-2A>C
A
C1QA|c.164-2
[u'NM_015991']
NM_015991:c.164-2A>C
NM_015991:c.164-2A>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PIK3CA:c.335T>A
T
PIK3CA|c.335
[u'NM_006218.2']
NM_006218.2:c.335T>A
NM_006218.2:c.335T>A
178916948
PLP1:c.454-9T>G
T
PLP1|c.454-9
[u'NM_000533.4']
NM_000533.4:c.454-9T>G
NM_000533.4:c.454-9T>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ALX3:c.661-1G>C
G
ALX3|c.661-1
[u'NM_006982.2']
NM_006982.2:c.661-1G>C
NM_006982.2:c.661-1G>C
85694932
{'end': 110604120, 'tr': 3, 'allele_string': [u'G', u'C'], 'start': 110604120, 'chr': u'1', 'strand': -1}
Frontonasal dysplasia (FND) is a heterogeneous group of disorders characterized by hypertelorism, telecanthus, broad nasal root, wide prominent nasal bridge, short and wide nasal ridge, broad columella and smooth philtrum. To date one X-linked and three autosomal recessive forms of FND have been reported in different ethnic groups. We sought to identify the gene responsible for FND in a consanguineous Pakistani family segregating the disorder in autosomal recessive pattern. Genome-wide homozygosity mapping using 250KNsp array revealed five homozygous regions in the selected affected individuals. Exome sequencing found a novel splice acceptor site variant (c.661-1G>C: NM_006982.2) in ALX1. Sanger sequencing confirmed the correct segregation of the pathogenic variant in the whole family. Our study concludes that the splice site variant identified in the ALX1 gene causes mild form of FND.
HEXA:c.1510C>T
C
HEXA|c.1510
[u'NM_000520.4']
NM_000520.4:c.1510C>T
NM_000520.4:c.1510C>T
72637803
CDK5RAP2:c.4114C>T
C
CDK5RAP2|c.4114
[u'XM_011518861.1']
XM_011518861.1:c.4114C>T
XM_011518861.1:c.4114C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
LGI1:c.1013T>C
T
LGI1|c.1013
[u'NM_005097.2']
NM_005097.2:c.1013T>C
NM_005097.2:c.1013T>C
95556899
MYBPC1:c.556G>A
G
MYBPC1|c.556
[u'NM_002465']
NM_002465:c.556G>A
NM_002465:c.556G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PAX6:c.2T>A
T
PAX6|c.2
[u'NG_008679.1']
NG_008679.1:c.2T>A
NG_008679.1:c.2T>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PAX6:c.2T>A
T
PAX6|c.2
[u'NG_008679.1']
NG_008679.1:c.2T>A
NG_008679.1:c.2T>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PTH1R:c.611T>A
T
PTH1R|c.611
[u'NM_000316']
NM_000316:c.611T>A
NM_000316:c.611T>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
REEP1:c.7GTAATAT>AC
GTAATAT
REEP1|c.7
[u'NM_022912']
NM_022912:c.7GTAATAT>AC
NM_022912:c.7GTAATAT>AC
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
FXN:g.41022153G>A
G
FXN|g.41022153
[u'NM_002875']
NM_002875:g.41022153G>A
NM_002875:g.41022153G>A
DATA RETURNED: None
TEXT RETURNED: null
None
GJA1:c.124G>C
G
GJA1|c.124
[u'NM_000165.3']
NM_000165.3:c.124G>C
NM_000165.3:c.124G>C
121768117
C9orf72:g.120962C>T
C
C9orf72|g.120962
[u'NG_007398.1']
NG_007398.1:g.120962C>T
NG_007398.1:g.120962C>T
DATA RETURNED: None
TEXT RETURNED: null
None
MAPT:c.750C>A
C
MAPT|c.750
[u'NG_007398.1']
NG_007398.1:c.750C>A
NG_007398.1:c.750C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CHCHD10:c.63C>T
C
CHCHD10|c.63
[u'NG_007398.1']
NG_007398.1:c.63C>T
NG_007398.1:c.63C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
TEAD1:c.71G>A
G
TEAD1|c.71
[u'NG_007398.1']
NG_007398.1:c.71G>A
NG_007398.1:c.71G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PHKG2:c.1963G>A
G
PHKG2|c.1963
[u'NM_000292.2']
NM_000292.2:c.1963G>A
NM_000292.2:c.1963G>A
18938150
{'end': 30769160, 'tr': 3, 'allele_string': [u'G', u'A'], 'start': 30769160, 'chr': u'16', 'strand': 1}
Glucogenosis type IX is caused by pathogenic variants of the PHKA2 gene. Herein, we report a patient with clinical symptoms compatible with Glycogen Storage Disease type IXa. PYGL, PHKA1, PHKA2, PHKB and PHKG2 genes were analyzed by Next Generation Sequencing (NGS). We identified the previously undescribed hemizygous missense variant NM_000292.2(PHKA2):c.1963G > A, p.(Glu655Lys) in PHKA2 exon 18. In silico analyses showed two possible pathogenic consequences: it affects a highly conserved amino acid and disrupts the exon 18 canonical splice donor site. The variant was found as a "de novo" event.
mtdna:c.323C>T
C
mtdna|c.323
[u'NM_004614.4']
NM_004614.4:c.323C>T
NM_004614.4:c.323C>T
66565335
OXSM:c.2750-1G>T
G
OXSM|c.2750-1
[u'NM_024757.4']
NM_024757.4:c.2750-1G>T
NM_024757.4:c.2750-1G>T
140705949
mtdna:m.4087A>G
A
mtdna|m.4087
[u'NC_012920.1']
NC_012920.1:m.4087A>G
NC_012920.1:m.4087A>G
Could not parse: ["NC_012920.1(TRNF_v001):n.*3440A>G", "NC_012920.1(RNR1_v001):n.*2486A>G", "NC_012920.1(TRNV_v001):n.*2417A>G", "NC_012920.1(RNR2_v001):n.*858A>G", "NC_012920.1(TRNL1_v001):n.*783A>G", "NC_012920.1(ND1_v001):c.781A>G", "NC_012920.1(TRNI_v001):n.-176A>G", "NC_012920.1(TRNQ_v001):n.*242T>C", "NC_012920.1(TRNM_v001):n.-315A>G", "NC_012920.1(ND2_v001):c.-383A>G", "NC_012920.1(TRNW_v001):n.-1425A>G", "NC_012920.1(TRNA_v001):n.*1500T>C", "NC_012920.1(TRNN_v001):n.*1570T>C", "NC_012920.1(TRNC_v001):n.*1674T>C", "NC_012920.1(TRNY_v001):n.*1739T>C", "NC_012920.1(COX1_v001):c.-1817A>G", "NC_012920.1(TRNS1_v001):n.*3359T>C", "NC_012920.1(TRND_v001):n.-3431A>G", "NC_012920.1(COX2_v001):c.-3499A>G", "NC_012920.1(TRNK_v001):n.-4208A>G", "NC_012920.1(ATP8_v001):c.-4279A>G", "NC_012920.1(ATP6_v001):c.-4440A>G"]
None
mtdna:m.4087A>G
A
mtdna|m.4087
[u'NC_012920.1']
NC_012920.1:m.4087A>G
NC_012920.1:m.4087A>G
Could not parse: ["NC_012920.1(TRNF_v001):n.*3440A>G", "NC_012920.1(RNR1_v001):n.*2486A>G", "NC_012920.1(TRNV_v001):n.*2417A>G", "NC_012920.1(RNR2_v001):n.*858A>G", "NC_012920.1(TRNL1_v001):n.*783A>G", "NC_012920.1(ND1_v001):c.781A>G", "NC_012920.1(TRNI_v001):n.-176A>G", "NC_012920.1(TRNQ_v001):n.*242T>C", "NC_012920.1(TRNM_v001):n.-315A>G", "NC_012920.1(ND2_v001):c.-383A>G", "NC_012920.1(TRNW_v001):n.-1425A>G", "NC_012920.1(TRNA_v001):n.*1500T>C", "NC_012920.1(TRNN_v001):n.*1570T>C", "NC_012920.1(TRNC_v001):n.*1674T>C", "NC_012920.1(TRNY_v001):n.*1739T>C", "NC_012920.1(COX1_v001):c.-1817A>G", "NC_012920.1(TRNS1_v001):n.*3359T>C", "NC_012920.1(TRND_v001):n.-3431A>G", "NC_012920.1(COX2_v001):c.-3499A>G", "NC_012920.1(TRNK_v001):n.-4208A>G", "NC_012920.1(ATP8_v001):c.-4279A>G", "NC_012920.1(ATP6_v001):c.-4440A>G"]
None
mtdna:m.4087A>G
A
mtdna|m.4087
[u'NC_012920.1']
NC_012920.1:m.4087A>G
NC_012920.1:m.4087A>G
Could not parse: ["NC_012920.1(TRNF_v001):n.*3440A>G", "NC_012920.1(RNR1_v001):n.*2486A>G", "NC_012920.1(TRNV_v001):n.*2417A>G", "NC_012920.1(RNR2_v001):n.*858A>G", "NC_012920.1(TRNL1_v001):n.*783A>G", "NC_012920.1(ND1_v001):c.781A>G", "NC_012920.1(TRNI_v001):n.-176A>G", "NC_012920.1(TRNQ_v001):n.*242T>C", "NC_012920.1(TRNM_v001):n.-315A>G", "NC_012920.1(ND2_v001):c.-383A>G", "NC_012920.1(TRNW_v001):n.-1425A>G", "NC_012920.1(TRNA_v001):n.*1500T>C", "NC_012920.1(TRNN_v001):n.*1570T>C", "NC_012920.1(TRNC_v001):n.*1674T>C", "NC_012920.1(TRNY_v001):n.*1739T>C", "NC_012920.1(COX1_v001):c.-1817A>G", "NC_012920.1(TRNS1_v001):n.*3359T>C", "NC_012920.1(TRND_v001):n.-3431A>G", "NC_012920.1(COX2_v001):c.-3499A>G", "NC_012920.1(TRNK_v001):n.-4208A>G", "NC_012920.1(ATP8_v001):c.-4279A>G", "NC_012920.1(ATP6_v001):c.-4440A>G"]
None
MT-ND1:c.781A>G
A
MT-ND1|c.781
[u'NC_012920.1']
NC_012920.1:c.781A>G
NC_012920.1:c.781A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
POLG:c.925C>T
C
POLG|c.925
[u'NM_002693.2']
NM_002693.2:c.925C>T
NM_002693.2:c.925C>T
89872272
POLG:c.2244G>T
G
POLG|c.2244
[u'NM_002693.2']
NM_002693.2:c.2244G>T
NM_002693.2:c.2244G>T
89866656
NDUFAF6:c.96046914T>C
T
NDUFAF6|c.96046914
[u'NM_152416.3']
NM_152416.3:c.96046914T>C
NM_152416.3:c.96046914T>C
192116077
NDUFAF6:c.298-768T>C
T
NDUFAF6|c.298-768
[u'NM_152416.3']
NM_152416.3:c.298-768T>C
NM_152416.3:c.298-768T>C
96046914
NDUFAF6:c.96046951A>G
A
NDUFAF6|c.96046951
[u'NM_152416.3']
NM_152416.3:c.96046951A>G
NM_152416.3:c.96046951A>G
192116114
NDUFAF6:c.298-731A>G
A
NDUFAF6|c.298-731
[u'NM_152416.3']
NM_152416.3:c.298-731A>G
NM_152416.3:c.298-731A>G
96046951
ELANE:c.401A>C
A
ELANE|c.401
[u'NM_001972.2']
NM_001972.2:c.401A>C
NM_001972.2:c.401A>C
855598
AVP:c.61T>C
T
AVP|c.61
[u'NM_000490.4']
NM_000490.4:c.61T>C
NM_000490.4:c.61T>C
3065260
GJB2:c.109G>A
G
GJB2|c.109
[u'NM_004004']
NM_004004:c.109G>A
NM_004004:c.109G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GJB2:c.109G>A
G
GJB2|c.109
[u'NM_004004']
NM_004004:c.109G>A
NM_004004:c.109G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GJB2:c.109G>A
G
GJB2|c.109
[u'NM_004004']
NM_004004:c.109G>A
NM_004004:c.109G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
TMEM231:c.784G>A
G
TMEM231|c.784
[u'NM_001077416.2']
NM_001077416.2:c.784G>A
NM_001077416.2:c.784G>A
75576539
TMEM231:c.406T>G
T
TMEM231|c.406
[u'NM_001077416.2']
NM_001077416.2:c.406T>G
NM_001077416.2:c.406T>G
75589764
TMTC1:c.460C>G
C
TMTC1|c.460
[u'NM_001200.3']
NM_001200.3:c.460C>G
NM_001200.3:c.460C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
TMTC1:c.584G>T
G
TMTC1|c.584
[u'NM_001200.3']
NM_001200.3:c.584G>T
NM_001200.3:c.584G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
NBAS:c.680A>C
A
NBAS|c.680
[u'NM_015909.3']
NM_015909.3:c.680A>C
NM_015909.3:c.680A>C
15674733
NBAS:c.1749G>A
G
NBAS|c.1749
[u'NM_015909.3']
NM_015909.3:c.1749G>A
NM_015909.3:c.1749G>A
15608634
COL5A1:c.4610G>T
G
COL5A1|c.4610
[u'NM_000093.4']
NM_000093.4:c.4610G>T
NM_000093.4:c.4610G>T
137714845
GATA3:c.856A>G
A
GATA3|c.856
[u'NM_001002295.1']
NM_001002295.1:c.856A>G
NM_001002295.1:c.856A>G
8106033
GATA3:c.1017C>G
C
GATA3|c.1017
[u'NM_001002295.1']
NM_001002295.1:c.1017C>G
NM_001002295.1:c.1017C>G
8111528
GATA3:c.896G>A
G
GATA3|c.896
[u'NM_001002295.1']
NM_001002295.1:c.896G>A
NM_001002295.1:c.896G>A
8106073
GATA3:c.1051-2A>G
A
GATA3|c.1051-2
[u'NM_001002295.1']
NM_001002295.1:c.1051-2A>G
NM_001002295.1:c.1051-2A>G
8115700
XYLT2:c.2188C>T
C
XYLT2|c.2188
[u'NM_022167.3']
NM_022167.3:c.2188C>T
NM_022167.3:c.2188C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
mtdna:g.2885C>A
C
mtdna|g.2885
[u'AC_000176']
AC_000176:g.2885C>A
AC_000176:g.2885C>A
DATA RETURNED: None
TEXT RETURNED: null
None
FLT4:c.3704C>G
C
FLT4|c.3704
[u'NM_182925.4']
NM_182925.4:c.3704C>G
NM_182925.4:c.3704C>G
180037008
mtdna:c.1442T>C
T
mtdna|c.1442
[u'NM_012160.4']
NM_012160.4:c.1442T>C
NM_012160.4:c.1442T>C
99323551
mtdna:c.1442T>C
T
mtdna|c.1442
[u'NM_012160.4']
NM_012160.4:c.1442T>C
NM_012160.4:c.1442T>C
99323551
mtdna:c.1442T>C
T
mtdna|c.1442
[u'NM_012160.4']
NM_012160.4:c.1442T>C
NM_012160.4:c.1442T>C
99323551
CHKB:c.810T>A
T
CHKB|c.810
[u'NM_005198.4']
NM_005198.4:c.810T>A
NM_005198.4:c.810T>A
51018627
GCNT2:c.85C>T
C
GCNT2|c.85
[u'NM_000202.7']
NM_000202.7:c.85C>T
NM_000202.7:c.85C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ATP7B:c.2335T>G
T
ATP7B|c.2335
[u'NG_008806.1']
NG_008806.1:c.2335T>G
NG_008806.1:c.2335T>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ATP7B:g.58164T>G
T
ATP7B|g.58164
[u'NG_008806.1']
NG_008806.1:g.58164T>G
NG_008806.1:g.58164T>G
DATA RETURNED: None
TEXT RETURNED: null
None
ATP7B:c.2335T>G
T
ATP7B|c.2335
[u'NG_008806.1']
NG_008806.1:c.2335T>G
NG_008806.1:c.2335T>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ATP7B:g.47964C>T
C
ATP7B|g.47964
[u'NG_008806.1']
NG_008806.1:g.47964C>T
NG_008806.1:g.47964C>T
DATA RETURNED: None
TEXT RETURNED: null
None
ATP7B:g.51482G>A
G
ATP7B|g.51482
[u'NG_008806.1']
NG_008806.1:g.51482G>A
NG_008806.1:g.51482G>A
DATA RETURNED: None
TEXT RETURNED: null
None
ATP7B:g.54622A>G
A
ATP7B|g.54622
[u'NG_008806.1']
NG_008806.1:g.54622A>G
NG_008806.1:g.54622A>G
DATA RETURNED: None
TEXT RETURNED: null
None
ATP7B:g.56255G>A
G
ATP7B|g.56255
[u'NG_008806.1']
NG_008806.1:g.56255G>A
NG_008806.1:g.56255G>A
DATA RETURNED: None
TEXT RETURNED: null
None
ATP7B:g.59042G>T
G
ATP7B|g.59042
[u'NG_008806.1']
NG_008806.1:g.59042G>T
NG_008806.1:g.59042G>T
DATA RETURNED: None
TEXT RETURNED: null
None
ATP7B:g.66363G>A
G
ATP7B|g.66363
[u'NG_008806.1']
NG_008806.1:g.66363G>A
NG_008806.1:g.66363G>A
DATA RETURNED: None
TEXT RETURNED: null
None
ATP7B:g.70004G>C
G
ATP7B|g.70004
[u'NG_008806.1']
NG_008806.1:g.70004G>C
NG_008806.1:g.70004G>C
DATA RETURNED: None
TEXT RETURNED: null
None
ATP7B:g.72244A>G
A
ATP7B|g.72244
[u'NG_008806.1']
NG_008806.1:g.72244A>G
NG_008806.1:g.72244A>G
DATA RETURNED: None
TEXT RETURNED: null
None
SLC6A9:c.1219A>G
A
SLC6A9|c.1219
[u'NM_201649.3']
NM_201649.3:c.1219A>G
NM_201649.3:c.1219A>G
44467262
WWOX:c.606-1G>A
G
WWOX|c.606-1
[u'NM_016373.3']
NM_016373.3:c.606-1G>A
NM_016373.3:c.606-1G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
Records: 10000
MYH8:c.2021G>A
G
MYH8|c.2021
[u'NM_002472.2']
NM_002472.2:c.2021G>A
NM_002472.2:c.2021G>A
10310241
GYS2:c.1720T>C
T
GYS2|c.1720
[u'NM_021957.3']
NM_021957.3:c.1720T>C
NM_021957.3:c.1720T>C
21693433
NF1:c.1466A>G
A
NF1|c.1466
[u'NM_000267.3']
NM_000267.3:c.1466A>G
NM_000267.3:c.1466A>G
29541542
NF1:c.1466A>G
A
NF1|c.1466
[u'NM_000267.3']
NM_000267.3:c.1466A>G
NM_000267.3:c.1466A>G
29541542
GJB2:c.2410T>C
T
GJB2|c.2410
[u'NM_004004.5']
NM_004004.5:c.2410T>C
NM_004004.5:c.2410T>C
20761311
GJB2:c.792T>C
T
GJB2|c.792
[u'NM_004004.5']
NM_004004.5:c.792T>C
NM_004004.5:c.792T>C
20762929
PIGP:c.74T>C
T
PIGP|c.74
[u'NM_153681.2']
NM_153681.2:c.74T>C
NM_153681.2:c.74T>C
38444814
AIP:c.910C>T
C
AIP|c.910
[u'NM_003977.3']
NM_003977.3:c.910C>T
NM_003977.3:c.910C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CTSC:c.899G>A
G
CTSC|c.899
[u'NM_001814.4']
NM_001814.4:c.899G>A
NM_001814.4:c.899G>A
88027667
TAS2R38:c.3413G>A
G
TAS2R38|c.3413
[u'NM_024757.4']
NM_024757.4:c.3413G>A
NM_024757.4:c.3413G>A
140711929
ASNS:c.970C>T
C
ASNS|c.970
[u'NM_001178076.1']
NM_001178076.1:c.970C>T
NM_001178076.1:c.970C>T
97483911
{'end': 97486062, 'tr': 1, 'allele_string': [u'C', u'T'], 'start': 97486062, 'chr': u'7', 'strand': -1}
Asparagine synthetase deficiency (OMIM# 615574) is a very rare newly described neurometabolic disorder characterized by congenital microcephaly and severe global developmental delay, associated with intractable seizures or hyperekplexia. Brain MRI typically shows cerebral atrophy with simplified gyral pattern and delayed myelination. Only 12 cases have been described to date. The disease is caused by homozygous or compound heterozygous mutations in the ASNS gene on chromosome 7q21.Family 1 is a multiplex consanguineous family with five affected members, while Family 2 is simplex. One affected from each family was available for detailed phenotyping. Both patients (Patients 1 and 2) presented at birth with microcephaly and severe hyperekplexia, and were found to have gross brain malformation characterized by simplified gyral pattern, and hypoplastic cerebellum and pons. EEG showed no epileptiform discharge in Patient 2 but multifocal discharges in patient 1. Patient 2 is currently four years old with severe neurodevelopmental delay, quadriplegia and cortical blindness. Whole exome sequencing (WES) revealed a novel homozygous mutation in ASNS (NM_001178076.1) in each patient (c.970C > T:p.(Arg324*) and c.944A > G:p.(Tyr315Cys)).Our results expand the mutational spectrum of the recently described asparagine synthetase deficiency and show a remarkable clinical homogeneity among affected individuals, which should facilitate its recognition and molecular confirmation for pertinent and timely genetic counseling.
ASNS:c.944A>G
A
ASNS|c.944
[u'NM_001178076.1']
NM_001178076.1:c.944A>G
NM_001178076.1:c.944A>G
97483937
MT-ATP6:c.2539G>A
G
MT-ATP6|c.2539
[u'NM_000188.2']
NM_000188.2:c.2539G>A
NM_000188.2:c.2539G>A
71158514
LMBR1:g.156584153A>G
A
LMBR1|g.156584153
[u'NC_000007.14']
NC_000007.14:g.156584153A>G
NC_000007.14:g.156584153A>G
DATA RETURNED: None
TEXT RETURNED: null
None
P4HB:c.1178A>G
A
P4HB|c.1178
[u'NM_000918.3']
NM_000918.3:c.1178A>G
NM_000918.3:c.1178A>G
79803618
HSD17B3:c.576G>A
G
HSD17B3|c.576
[u'NM_000197.1']
NM_000197.1:c.576G>A
NM_000197.1:c.576G>A
99007657
SCN9A:c.5218G>C
G
SCN9A|c.5218
[u'NM_002977']
NM_002977:c.5218G>C
NM_002977:c.5218G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
YARS:c.638C>T
C
YARS|c.638
[u'NM_003680.3']
NM_003680.3:c.638C>T
NM_003680.3:c.638C>T
33256809
YARS:c.1573G>A
G
YARS|c.1573
[u'NM_003680.3']
NM_003680.3:c.1573G>A
NM_003680.3:c.1573G>A
33241596
SH2B2:c.6G>A
G
SH2B2|c.6
[u'NM_000383.2']
NM_000383.2:c.6G>A
NM_000383.2:c.6G>A
45705895
ALS2:c.3512+1G>A
G
ALS2|c.3512+1
[u'NM_020919.3']
NM_020919.3:c.3512+1G>A
NM_020919.3:c.3512+1G>A
202589017
NF1:c.3113+1G>A
G
NF1|c.3113+1
[u'NM_000267.3']
NM_000267.3:c.3113+1G>A
NM_000267.3:c.3113+1G>A
29557401
ARX:c.1614G>T
G
ARX|c.1614
[u'NM_139058.2']
NM_139058.2:c.1614G>T
NM_139058.2:c.1614G>T
25022862
FGFR3:c.1637C>A
C
FGFR3|c.1637
[u'NM_000142.4']
NM_000142.4:c.1637C>A
NM_000142.4:c.1637C>A
1807388
{'end': 1807382, 'tr': 1, 'allele_string': [u'C', u'A'], 'start': 1807382, 'chr': u'4', 'strand': 1}
Most reported mutations in the FGFR3 gene are dominant activating mutations that cause a variety of short-limbed bone dysplasias including achondroplasia and syndromic craniosynostosis. We report the phenotype and underlying molecular abnormality in two brothers, born to first cousin parents. The clinical picture is characterized by tall stature and severe skeletal abnormalities leading to inability to walk, with camptodactyly, arachnodactyly, and scoliosis. Whole exome sequencing revealed a homozygous novel missense mutation in the FGFR3 gene in exon 12 (NM_000142.4:c.1637C>A: p.(Thr546Lys)). The variant is found in the kinase domain of the protein and is predicted to be pathogenic. It is located near a known hotspot for hypochondroplasia. This is the first report of a homozygous loss-of-function mutation in FGFR3 in human that results in a skeletal overgrowth syndrome.
MYOD1:c.188C>A
C
MYOD1|c.188
[u'NM_002478.4']
NM_002478.4:c.188C>A
NM_002478.4:c.188C>A
17741517
ROGDI:c.117+1G>T
G
ROGDI|c.117+1
[u'NM_024589.1']
NM_024589.1:c.117+1G>T
NM_024589.1:c.117+1G>T
4852382
ROGDI:g.4852382C>A
C
ROGDI|g.4852382
[u'NM_024589.1']
NM_024589.1:g.4852382C>A
NM_024589.1:g.4852382C>A
DATA RETURNED: None
TEXT RETURNED: null
None
PCBD1:c.2609G>A
G
PCBD1|c.2609
[u'NM_001243342.1']
NM_001243342.1:c.2609G>A
NM_001243342.1:c.2609G>A
78061565
SLC12A3:c.1095+5G>A
G
SLC12A3|c.1095+5
[u'NM_000339.2']
NM_000339.2:c.1095+5G>A
NM_000339.2:c.1095+5G>A
56906703
POLE:c.1089C>A
C
POLE|c.1089
[u'NM_006231.2']
NM_006231.2:c.1089C>A
NM_006231.2:c.1089C>A
133252338
L1CAM:c.604G>A
G
L1CAM|c.604
[u'NM_000425.3']
NM_000425.3:c.604G>A
NM_000425.3:c.604G>A
153136335
CCDC151:c.925G>T
G
CCDC151|c.925
[u'NM_145045.4']
NM_145045.4:c.925G>T
NM_145045.4:c.925G>T
11537002
CDKL5:c.533G>A
G
CDKL5|c.533
[u'NM_003159.2']
NM_003159.2:c.533G>A
NM_003159.2:c.533G>A
18602452
CDKL5:c.1A>G
A
CDKL5|c.1
[u'NM_003159.2']
NM_003159.2:c.1A>G
NM_003159.2:c.1A>G
18525217
CDKL5:c.1A>G
A
CDKL5|c.1
[u'NM_003159.2']
NM_003159.2:c.1A>G
NM_003159.2:c.1A>G
18525217
CDKL5:c.1375C>T
C
CDKL5|c.1375
[u'NM_003159.2']
NM_003159.2:c.1375C>T
NM_003159.2:c.1375C>T
18622419
WISP3:c.156C>A
C
WISP3|c.156
[u'NP_003871.1']
NP_003871.1:c.156C>A
NP_003871.1:c.156C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
WISP3:c.643+1G>A
G
WISP3|c.643+1
[u'NP_003871.1']
NP_003871.1:c.643+1G>A
NP_003871.1:c.643+1G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
KCNJ13:c.359T>C
T
KCNJ13|c.359
[u'NM_002242.4']
NM_002242.4:c.359T>C
NM_002242.4:c.359T>C
233635714
CAPN3:c.1524+1G>T
G
CAPN3|c.1524+1
[u'NM_000070']
NM_000070:c.1524+1G>T
NM_000070:c.1524+1G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CAPN3:c.1524+1G>T
G
CAPN3|c.1524+1
[u'NM_000070']
NM_000070:c.1524+1G>T
NM_000070:c.1524+1G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CAPN3:c.2384C>T
C
CAPN3|c.2384
[u'NM_000070']
NM_000070:c.2384C>T
NM_000070:c.2384C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
COL4A3:c.3266G>A
G
COL4A3|c.3266
[u'NM_000091.4']
NM_000091.4:c.3266G>A
NM_000091.4:c.3266G>A
228157962
STIM1:c.910C>T
C
STIM1|c.910
[u'NM_003156.3']
NM_003156.3:c.910C>T
NM_003156.3:c.910C>T
4095850
STIM1:c.910C>T
C
STIM1|c.910
[u'NM_003156.3']
NM_003156.3:c.910C>T
NM_003156.3:c.910C>T
4095850
DMP1:c.1A>G
A
DMP1|c.1
[u'NM_001079911.2']
NM_001079911.2:c.1A>G
NM_001079911.2:c.1A>G
88577645
B4GALT7:c.808C>T
C
B4GALT7|c.808
[u'NM_007255.2']
NM_007255.2:c.808C>T
NM_007255.2:c.808C>T
177035995
MPV17:c.278A>C
A
MPV17|c.278
[u'NM_002437.4']
NM_002437.4:c.278A>C
NM_002437.4:c.278A>C
27535548
GNAS:c.682C>T
C
GNAS|c.682
[u'NM_000516.4']
NM_000516.4:c.682C>T
NM_000516.4:c.682C>T
57484598
{'end': 57429002, 'tr': 2, 'allele_string': [u'C', u'T'], 'start': 57429002, 'chr': u'20', 'strand': 1}
Pseudohypoparathyroidism is a rare genetic disorder characterised by end-organ resistance to parathyroid hormone due to a defect of the guanine nucleotide-binding protein alpha that simulates activity of the polypeptide 1 (GNAS) gene. Patients with type 1a pseudohypoparathyroidism display different features of Albright's hereditary osteodystrophy as well as multi-hormone resistance. We describe a Chinese woman and her son, who presented with different symptoms of pseudohypoparathyroidism and clinically manifested different degree of Albright's hereditary osteodystrophy. Genetic study detected a mutation [NM_000516.4(GNAS):c682C>T (p.Arg228Cys)] in the GNAS gene.
FGF23:c.471C>A
C
FGF23|c.471
[u'NM_020638.2']
NM_020638.2:c.471C>A
NM_020638.2:c.471C>A
4479794
RS1:c.304C>T
C
RS1|c.304
[u'NM_000330.3']
NM_000330.3:c.304C>T
NM_000330.3:c.304C>T
18665333
MCDR3:c.139G>A
G
MCDR3|c.139
[u'NM_001278634']
NM_001278634:c.139G>A
NM_001278634:c.139G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HFE:c.847C>T
C
HFE|c.847
[u'NM_000410.3']
NM_000410.3:c.847C>T
NM_000410.3:c.847C>T
26093143
ADSL:c.71C>T
C
ADSL|c.71
[u'NM_000026']
NM_000026:c.71C>T
NM_000026:c.71C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ADSL:c.134G>A
G
ADSL|c.134
[u'NM_000026']
NM_000026:c.134G>A
NM_000026:c.134G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
DTNBP1:c.307C>T
C
DTNBP1|c.307
[u'NM_032122.4']
NM_032122.4:c.307C>T
NM_032122.4:c.307C>T
15627622
NEU1:c.699C>A
C
NEU1|c.699
[u'NM_000434.3']
NM_000434.3:c.699C>A
NM_000434.3:c.699C>A
31828315
NEU1:c.803A>G
A
NEU1|c.803
[u'NM_000434.3']
NM_000434.3:c.803A>G
NM_000434.3:c.803A>G
31828037
CHKB:c.810T>A
T
CHKB|c.810
[u'NM_005198.4']
NM_005198.4:c.810T>A
NM_005198.4:c.810T>A
51018627
ZNF644:c.1201A>G
A
ZNF644|c.1201
[u'NM_201269']
NM_201269:c.1201A>G
NM_201269:c.1201A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ZNF644:c.2867C>G
C
ZNF644|c.2867
[u'NM_201269']
NM_201269:c.2867C>G
NM_201269:c.2867C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ZNF644:c.3833A>G
A
ZNF644|c.3833
[u'NM_201269']
NM_201269:c.3833A>G
NM_201269:c.3833A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ZNF644:c.2565A>G
A
ZNF644|c.2565
[u'NM_201269']
NM_201269:c.2565A>G
NM_201269:c.2565A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ZNF644:c.219C>A
C
ZNF644|c.219
[u'NM_201269']
NM_201269:c.219C>A
NM_201269:c.219C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ZNF644:c.3833A>G
A
ZNF644|c.3833
[u'NM_201269']
NM_201269:c.3833A>G
NM_201269:c.3833A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PAX9:c.87G>C
G
PAX9|c.87
[u'NC_000014']
NC_000014:c.87G>C
NC_000014:c.87G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PAX9:c.87G>C
G
PAX9|c.87
[u'NC_000014']
NC_000014:c.87G>C
NC_000014:c.87G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
RINT1:c.343C>T
C
RINT1|c.343
[u'NM_021930.4']
NM_021930.4:c.343C>T
NM_021930.4:c.343C>T
105182924
RINT1:c.1207G>T
G
RINT1|c.1207
[u'NM_021930.4']
NM_021930.4:c.1207G>T
NM_021930.4:c.1207G>T
105190807
SLC25A13:c.615+5G>A
G
SLC25A13|c.615+5
[u'NM_138459.3']
NM_138459.3:c.615+5G>A
NM_138459.3:c.615+5G>A
118015272
{'end': 95822344, 'tr': 1, 'allele_string': [u'G', u'A'], 'start': 95822344, 'chr': u'7', 'strand': -1}
To investigate the differences in the mutation spectra of the SLC25A13 gene mutations from specific regions of China.Genetic analyses of SLC25A13 mutations were performed in 535 patients with neonatal intrahepatic cholestasis from our center over eight years. Unrelated infants with at least one mutant allele were enrolled to calculate the proportion of SLC25A13 mutations in different regions of China. The boundary between northern and southern China was drawn at the historical border of the Yangtze River.A total of 63 unrelated patients (about 11% of cases with intrahepatic cholestasis) from 16 provinces or municipalities in China had mutations in the SLC25A13 gene, of these 16 (25%) were homozygotes, 28 (44%) were compound heterozygotes and 19 (30%) were heterozygotes. In addition to four well described common mutations (c.851_854del, c.1638_1660dup23, c.615+5G>A and c.1750+72_1751-4dup17insNM_138459.3:2667 also known as IVS16ins3kb), 13 other mutation types were identified, including three novel mutations: c.985_986insT, c.287T>C and c.1349A>G. According to the geographical division criteria, 60 mutant alleles were identified in patients from the southern areas of China, 43 alleles were identified in patients from the border, and 4 alleles were identified in patients from the northern areas of China. The proportion of four common mutations was higher in south region (56/60, 93%) than that in the border region (34/43, 79%, χ(2) = 4.621, P = 0.032) and the northern region (2/4, 50%, χ(2) = 8.288, P = 0.041).The SLC25A13 mutation spectra among the three regions of China were different, providing a basis for the improvement of diagnostic strategies and interpretation of genetic diagnosis.
SLC25A13:c.287T>C
T
SLC25A13|c.287
[u'NM_138459.3']
NM_138459.3:c.287T>C
NM_138459.3:c.287T>C
117997120
{'end': 95864155, 'tr': 1, 'allele_string': [u'T', u'C'], 'start': 95864155, 'chr': u'7', 'strand': -1}
To investigate the differences in the mutation spectra of the SLC25A13 gene mutations from specific regions of China.Genetic analyses of SLC25A13 mutations were performed in 535 patients with neonatal intrahepatic cholestasis from our center over eight years. Unrelated infants with at least one mutant allele were enrolled to calculate the proportion of SLC25A13 mutations in different regions of China. The boundary between northern and southern China was drawn at the historical border of the Yangtze River.A total of 63 unrelated patients (about 11% of cases with intrahepatic cholestasis) from 16 provinces or municipalities in China had mutations in the SLC25A13 gene, of these 16 (25%) were homozygotes, 28 (44%) were compound heterozygotes and 19 (30%) were heterozygotes. In addition to four well described common mutations (c.851_854del, c.1638_1660dup23, c.615+5G>A and c.1750+72_1751-4dup17insNM_138459.3:2667 also known as IVS16ins3kb), 13 other mutation types were identified, including three novel mutations: c.985_986insT, c.287T>C and c.1349A>G. According to the geographical division criteria, 60 mutant alleles were identified in patients from the southern areas of China, 43 alleles were identified in patients from the border, and 4 alleles were identified in patients from the northern areas of China. The proportion of four common mutations was higher in south region (56/60, 93%) than that in the border region (34/43, 79%, χ(2) = 4.621, P = 0.032) and the northern region (2/4, 50%, χ(2) = 8.288, P = 0.041).The SLC25A13 mutation spectra among the three regions of China were different, providing a basis for the improvement of diagnostic strategies and interpretation of genetic diagnosis.
SLC25A13:c.1349A>G
A
SLC25A13|c.1349
[u'NM_138459.3']
NM_138459.3:c.1349A>G
NM_138459.3:c.1349A>G
118028645
MRE11:c.140C>T
C
MRE11|c.140
[u'NM_005590']
NM_005590:c.140C>T
NM_005590:c.140C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ACVR1:c.617G>A
G
ACVR1|c.617
[u'NM_001105.4']
NM_001105.4:c.617G>A
NM_001105.4:c.617G>A
158630626
mtdna:c.665G>C
G
mtdna|c.665
[u'NM_001079855']
NM_001079855:c.665G>C
NM_001079855:c.665G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
BBS2:c.173T>G
T
BBS2|c.173
[u'NM_001195306']
NM_001195306:c.173T>G
NM_001195306:c.173T>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MED12:c.1862G>A
G
MED12|c.1862
[u'NM_005120.2']
NM_005120.2:c.1862G>A
NM_005120.2:c.1862G>A
70344126
TGM6:c.1550T>G
T
TGM6|c.1550
[u'NM_198994.2']
NM_198994.2:c.1550T>G
NM_198994.2:c.1550T>G
2398091
MTSS1:c.532A>T
A
MTSS1|c.532
[u'NM_005159.4']
NM_005159.4:c.532A>T
NM_005159.4:c.532A>T
35084693
G6PC3:c.974T>G
T
G6PC3|c.974
[u'NM_138387.3']
NM_138387.3:c.974T>G
NM_138387.3:c.974T>G
42153344
VLDLR:c.665C>T
C
VLDLR|c.665
[u'NM_178153.2']
NM_178153.2:c.665C>T
NM_178153.2:c.665C>T
110644258
{'end': 2643376, 'tr': 2, 'allele_string': [u'C', u'T'], 'start': 2643376, 'chr': u'9', 'strand': 1}
Malformations of cortical development include a wide range of brain developmental anomalies that commonly lead to developmental delay and epilepsy. Lissencephaly and subcortical band heterotopia are major malformations of cortical development due to abnormal neuronal migration and several genes have been identified including ARX, DCX, LIS1, RELN, TUBA1A, and VLDLR. Traditionally, genetic testing for lissencephaly and subcortical band heterotopia has been done in the order of the probability of detection of mutation according to the radiologic features, but the success rate could be variable with this time-consuming approach. In this study we used whole-exome sequencing to identify mutations in a 5-year-old girl with lissencephaly spectrum with subcortical band heterotopia. After excluding lissencephaly-related genes, one deleterious mutation (NM_178153.2:c.665C > T, p.Thr222Ile) in the DCX gene was identified. Further Sanger sequencing validated the variant in the patient but not in both parents indicating a de novo mutation. The present report demonstrates that whole-exome sequencing may be a useful tool for the identification of mutations in patients with lissencephaly and subcortical band heterotopias as well as malformations of cortical development.
XPC:g.18246G>A
G
XPC|g.18246
[u'NG_011763.1']
NG_011763.1:g.18246G>A
NG_011763.1:g.18246G>A
DATA RETURNED: None
TEXT RETURNED: null
None
XPC:g.18810G>T
G
XPC|g.18810
[u'NG_011763.1']
NG_011763.1:g.18810G>T
NG_011763.1:g.18810G>T
DATA RETURNED: None
TEXT RETURNED: null
None
NKX2-1:c.516G>T
G
NKX2-1|c.516
[u'NM_003317.3']
NM_003317.3:c.516G>T
NM_003317.3:c.516G>T
36987083
NKX2-1:c.623G>C
G
NKX2-1|c.623
[u'NM_003317.3']
NM_003317.3:c.623G>C
NM_003317.3:c.623G>C
36986976
{'end': 36987066, 'tr': 4, 'allele_string': [u'G', u'C'], 'start': 36987066, 'chr': u'14', 'strand': -1}
The thyroid transcription factor 1 (TTF-1) is encoded, on chromosome 14q13, by the gene termed TITF-1/NKX2.1. Mutations in this gene have been associated with chorea, hypothyroidism, and lung disease, all included in the "brain-thyroid-lung syndrome." We here describe two cases of novel missense mutations [NM_003317.3:c.516G>T and c.623G>C resulting in p.(Gln172His) and p.(Trp208Ser), respectively] in TITF-1/NKX2-1 in non-consanguineous patients. We provide a functional study of the role of the two mutations on the TTF-1 ability to bind DNA and to trans-activate both thyroid and lung specific gene promoters. Our results confirm the difficulty to correlate the TTF-1 activity with the clinical phenotype of affected patients and highlight the need to increase the limited knowledge we have on the activity of TTF-1 in neuronal cells.
YAP1:c.370C>T
C
YAP1|c.370
[u'NM_001130145']
NM_001130145:c.370C>T
NM_001130145:c.370C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
YAP1:c.1066G>T
G
YAP1|c.1066
[u'NM_001130145']
NM_001130145:c.1066G>T
NM_001130145:c.1066G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
YAP1:c.370C>T
C
YAP1|c.370
[u'NM_001130145']
NM_001130145:c.370C>T
NM_001130145:c.370C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
YAP1:c.1066G>T
G
YAP1|c.1066
[u'NM_001130145']
NM_001130145:c.1066G>T
NM_001130145:c.1066G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SHH:g.106737G>T
G
SHH|g.106737
[u'NG_009240.1']
NG_009240.1:g.106737G>T
NG_009240.1:g.106737G>T
DATA RETURNED: None
TEXT RETURNED: null
None
LMBR1:c.404G>T
G
LMBR1|c.404
[u'NG_009240.1']
NG_009240.1:c.404G>T
NG_009240.1:c.404G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ALDH5A1:c.901A>G
A
ALDH5A1|c.901
[u'NM_001080']
NM_001080:c.901A>G
NM_001080:c.901A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
KALRN:c.3644C>A
C
KALRN|c.3644
[u'NM_003947.4']
NM_003947.4:c.3644C>A
NM_003947.4:c.3644C>A
124174121
SRY:c.341A>G
A
SRY|c.341
[u'NM_005634']
NM_005634:c.341A>G
NM_005634:c.341A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SMS:c.443A>G
A
SMS|c.443
[u'NM_004595.4']
NM_004595.4:c.443A>G
NM_004595.4:c.443A>G
21995292
CD4:g.70A>G
A
CD4|g.70
[u'NR_003051']
NR_003051:g.70A>G
NR_003051:g.70A>G
DATA RETURNED: None
TEXT RETURNED: null
None
MOGS:c.65C>A
C
MOGS|c.65
[u'NM_006302.2']
NM_006302.2:c.65C>A
NM_006302.2:c.65C>A
74692310
MOGS:c.329G>A
G
MOGS|c.329
[u'NM_006302.2']
NM_006302.2:c.329G>A
NM_006302.2:c.329G>A
74692046
MOGS:c.370C>T
C
MOGS|c.370
[u'NM_006302.2']
NM_006302.2:c.370C>T
NM_006302.2:c.370C>T
74691832
HSP90AA1:g.1209A>G
A
HSP90AA1|g.1209
[u'AC_000178.1']
AC_000178.1:g.1209A>G
AC_000178.1:g.1209A>G
DATA RETURNED: None
TEXT RETURNED: null
None
HSP90AA1:g.1209A>G
A
HSP90AA1|g.1209
[u'AC_000178.1']
AC_000178.1:g.1209A>G
AC_000178.1:g.1209A>G
DATA RETURNED: None
TEXT RETURNED: null
None
TTN:c.90263G>T
G
TTN|c.90263
[u'NM_001256850']
NM_001256850:c.90263G>T
NM_001256850:c.90263G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
EHMT1:c.2712+1G>A
G
EHMT1|c.2712+1
[u'NM_024757.4']
NM_024757.4:c.2712+1G>A
NM_024757.4:c.2712+1G>A
140695437
EHMT1:c.2712+1G>A
G
EHMT1|c.2712+1
[u'NM_024757.4']
NM_024757.4:c.2712+1G>A
NM_024757.4:c.2712+1G>A
140695437
CAPN1:g.98533962C>G
C
CAPN1|g.98533962
[u'NM_174003']
NM_174003:g.98533962C>G
NM_174003:g.98533962C>G
DATA RETURNED: None
TEXT RETURNED: null
None
CAPN1:g.98535683A>G
A
CAPN1|g.98535683
[u'NM_174003']
NM_174003:g.98535683A>G
NM_174003:g.98535683A>G
DATA RETURNED: None
TEXT RETURNED: null
None
CAPN1:g.98545188T>A
T
CAPN1|g.98545188
[u'NM_174003']
NM_174003:g.98545188T>A
NM_174003:g.98545188T>A
DATA RETURNED: None
TEXT RETURNED: null
None
CAPN1:g.98535683A>G
A
CAPN1|g.98535683
[u'NM_174003']
NM_174003:g.98535683A>G
NM_174003:g.98535683A>G
DATA RETURNED: None
TEXT RETURNED: null
None
PSMC3IP:c.337+33A>G
A
PSMC3IP|c.337+33
[u'NM_016556.3']
NM_016556.3:c.337+33A>G
NM_016556.3:c.337+33A>G
40726084
GLDC:c.2296G>T
G
GLDC|c.2296
[u'NM_000170.2']
NM_000170.2:c.2296G>T
NM_000170.2:c.2296G>T
6554688
SLC17A5:c.526-2A>G
A
SLC17A5|c.526-2
[u'NM_012434']
NM_012434:c.526-2A>G
NM_012434:c.526-2A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PIGT:c.1342C>T
C
PIGT|c.1342
[u'NM_015937.5']
NM_015937.5:c.1342C>T
NM_015937.5:c.1342C>T
44052963
ERCC6:c.2008C>T
C
ERCC6|c.2008
[u'NM_000124.2']
NM_000124.2:c.2008C>T
NM_000124.2:c.2008C>T
50690894
HOXD3:c.543-199G>T
G
HOXD3|c.543-199
[u'NP_008829.3']
NP_008829.3:c.543-199G>T
NP_008829.3:c.543-199G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HOXD3:c.543-34G>A
G
HOXD3|c.543-34
[u'NP_008829.3']
NP_008829.3:c.543-34G>A
NP_008829.3:c.543-34G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PITX2:c.45+76C>T
C
PITX2|c.45+76
[u'NP_008829.3']
NP_008829.3:c.45+76C>T
NP_008829.3:c.45+76C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
NF2:g.74409T>A
T
NF2|g.74409
[u'NG_009057.1']
NG_009057.1:g.74409T>A
NG_009057.1:g.74409T>A
DATA RETURNED: None
TEXT RETURNED: null
None
LZTFL1:c.260T>C
T
LZTFL1|c.260
[u'NM_020347.2']
NM_020347.2:c.260T>C
NM_020347.2:c.260T>C
45877145
LZTFL1:c.778G>T
G
LZTFL1|c.778
[u'NM_020347.2']
NM_020347.2:c.778G>T
NM_020347.2:c.778G>T
45868951
CAPN1:g.98533962C>G
C
CAPN1|g.98533962
[u'NM_174003']
NM_174003:g.98533962C>G
NM_174003:g.98533962C>G
DATA RETURNED: None
TEXT RETURNED: null
None
CAPN1:g.98535683A>G
A
CAPN1|g.98535683
[u'NM_174003']
NM_174003:g.98535683A>G
NM_174003:g.98535683A>G
DATA RETURNED: None
TEXT RETURNED: null
None
CAPN1:g.98545188T>A
T
CAPN1|g.98545188
[u'NM_174003']
NM_174003:g.98545188T>A
NM_174003:g.98545188T>A
DATA RETURNED: None
TEXT RETURNED: null
None
CAPN1:g.98535683A>G
A
CAPN1|g.98535683
[u'NM_174003']
NM_174003:g.98535683A>G
NM_174003:g.98535683A>G
DATA RETURNED: None
TEXT RETURNED: null
None
PAEP:c.1448T>C
T
PAEP|c.1448
[u'NM_000157.3']
NM_000157.3:c.1448T>C
NM_000157.3:c.1448T>C
155205043
RECQL4:c.2059-1G>C
G
RECQL4|c.2059-1
[u'NM_004260']
NM_004260:c.2059-1G>C
NM_004260:c.2059-1G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SMARCB1:c.359T>C
T
SMARCB1|c.359
[u'NM_001040108.1']
NM_001040108.1:c.359T>C
NM_001040108.1:c.359T>C
75516000
{'end': 24135872, 'tr': 1, 'allele_string': [u'T', u'C'], 'start': 24135872, 'chr': u'22', 'strand': 1}
A 4-month-old male infant presented with severe developmental delay, cerebellar, brainstem, and cutaneous hemangiomas, bilateral tumors (vestibular, hypoglossal, cervical, and lumbar spinal), and few café-au-lait macules. Cerebellar and lumbar tumor biopsies revealed venous telangiectasia and intraneural perineuroma, respectively. Sequencing NF1, NF2, and RASA1 (blood), and NF2 and SMARCB1 (lumbar biopsy) was negative for pathogenic mutations. Clinical exome sequencing (CES), requested for tumor syndrome diagnosis, revealed two heterozygous missense variants, c.359T>C;p.Phe120Ser and c.3344G>A;p.Arg1115Gln, in MLH3 (NM_001040108.1), a DNA mismatch repair (MMR) gene, Polyphen-predicted as probably damaging, and benign, respectively. Sanger sequencing confirmed both variants in the proband, and their absence in the mother; biological father unavailable. Both biopsied tissues were negative for microsatellite instability, and expressed MLH1, MSH2, PMS2, MSH6, and MLH3 immunohistochemically. Chromosomal microarray showed a 133 kb segment copy number duplication of 14q12 region encompassing FOXG1, possibly explaining the developmental delay, but not the tumors. The presence of MLH3 variants with multiple benign neural and vascular tumors was intriguing for their possible role in the pathogenesis of these neoplasms, which were suspicious for, but not diagnostic of, constitutional MMR deficiency. However, functional assays of non-neoplastic patient-derived cells showed intact base-base MMR function. Also, no previous FOXG1-aberrant patient was reported with tumors. We now report a 3-year-old FOXG1-duplicated patient with a yet undescribed tumor syndrome with clinical features of neurofibromatosis types I and II, where several validation studies could not ascertain the significance of CES findings; further studies may elucidate precise mechanisms and diagnosis for clinical management, including tumor surveillance.
SMARCB1:c.3344G>A
G
SMARCB1|c.3344
[u'NM_001040108.1']
NM_001040108.1:c.3344G>A
NM_001040108.1:c.3344G>A
75509117
LMBR1:g.106954C>T
C
LMBR1|g.106954
[u'NG_009240.1']
NG_009240.1:g.106954C>T
NG_009240.1:g.106954C>T
DATA RETURNED: None
TEXT RETURNED: null
None
LMBR1:c.619C>T
C
LMBR1|c.619
[u'NG_009240.1']
NG_009240.1:c.619C>T
NG_009240.1:c.619C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
STUB1:c.621C>G
C
STUB1|c.621
[u'NM_005861']
NM_005861:c.621C>G
NM_005861:c.621C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
TPO:c.2669G>A
G
TPO|c.2669
[u'NM_000547.5']
NM_000547.5:c.2669G>A
NM_000547.5:c.2669G>A
1544416
OTOF:c.5332G>T
G
OTOF|c.5332
[u'NM_194248.2']
NM_194248.2:c.5332G>T
NM_194248.2:c.5332G>T
26684765
OTOF:c.5332G>T
G
OTOF|c.5332
[u'NM_194248.2']
NM_194248.2:c.5332G>T
NM_194248.2:c.5332G>T
26684765
PRIMPOL:c.265T>G
T
PRIMPOL|c.265
[u'NM_152683.2']
NM_152683.2:c.265T>G
NM_152683.2:c.265T>G
185580578
MFN2:c.1066A>G
A
MFN2|c.1066
[u'NM_014874.3']
NM_014874.3:c.1066A>G
NM_014874.3:c.1066A>G
12062066
KAT6A:c.4108G>T
G
KAT6A|c.4108
[u'NM_001099412.1']
NM_001099412.1:c.4108G>T
NM_001099412.1:c.4108G>T
41791630
Records: 20000
BMP15:g.1773T>C
T
BMP15|g.1773
[u'NC_006091.3']
NC_006091.3:g.1773T>C
NC_006091.3:g.1773T>C
DATA RETURNED: None
TEXT RETURNED: null
None
GCK:c.878T>C
T
GCK|c.878
[u'NM_000162.3']
NM_000162.3:c.878T>C
NM_000162.3:c.878T>C
44186203
{'end': 44186206, 'tr': 1, 'allele_string': [u'T', u'C'], 'start': 44186206, 'chr': u'7', 'strand': -1}
Maturity-onset diabetes of the young type 2 (MODY2) is an autosomal dominant inherited disease caused by heterozygous inactivating mutations in the glucokinase (GCK) gene and is characterized by mild noninsulin-dependent fasting hyperglycemia. It is treated with diet only, and complications are extremely rare. We present a report of a family with MODY2 caused by a novel NM_000162.3:c.878T>C mutation in exon 8 of the GCK gene. Testing for MODY2 and reporting all novel mutations are important to avoid difficulties in the interpretation of genetic test results and to provide fast and definitive diagnosis for all patients with this disease.
DMD:c.10141C>T
C
DMD|c.10141
[u'NM_004006.1']
NM_004006.1:c.10141C>T
NM_004006.1:c.10141C>T
31196868
SLC25A1:c.593G>A
G
SLC25A1|c.593
[u'NM_005984.4']
NM_005984.4:c.593G>A
NM_005984.4:c.593G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ERCC8:c.618-2A>G
A
ERCC8|c.618-2
[u'NM_000082']
NM_000082:c.618-2A>G
NM_000082:c.618-2A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GCNT2:g.8662T>C
T
GCNT2|g.8662
[u'NG_011595.1']
NG_011595.1:g.8662T>C
NG_011595.1:g.8662T>C
DATA RETURNED: None
TEXT RETURNED: null
None
GCNT2:g.8662T>C
T
GCNT2|g.8662
[u'NG_011595.1']
NG_011595.1:g.8662T>C
NG_011595.1:g.8662T>C
DATA RETURNED: None
TEXT RETURNED: null
None
ARV1:c.294+1G>A
G
ARV1|c.294+1
[u'NP_073623.1']
NP_073623.1:c.294+1G>A
NP_073623.1:c.294+1G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
COL5A1:c.2A>G
A
COL5A1|c.2
[u'NM_000093.3']
NM_000093.3:c.2A>G
NM_000093.3:c.2A>G
137534035
COL5A1:c.2A>G
A
COL5A1|c.2
[u'NM_000093.3']
NM_000093.3:c.2A>G
NM_000093.3:c.2A>G
137534035
PAH:c.6T>A
T
PAH|c.6
[u'NM_000277']
NM_000277:c.6T>A
NM_000277:c.6T>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PAH:c.2A>G
A
PAH|c.2
[u'NM_000277']
NM_000277:c.2A>G
NM_000277:c.2A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PAH:c.1G>A
G
PAH|c.1
[u'NM_000277']
NM_000277:c.1G>A
NM_000277:c.1G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PAH:c.5G>C
G
PAH|c.5
[u'NM_000277']
NM_000277:c.5G>C
NM_000277:c.5G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SMARCAD1:c.378+1G>T
G
SMARCAD1|c.378+1
[u'NG_031945.1']
NG_031945.1:c.378+1G>T
NG_031945.1:c.378+1G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PGAP2:c.46C>T
C
PGAP2|c.46
[u'NP_001243169.1']
NP_001243169.1:c.46C>T
NP_001243169.1:c.46C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PGAP2:c.380T>C
T
PGAP2|c.380
[u'NP_001243169.1']
NP_001243169.1:c.380T>C
NP_001243169.1:c.380T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PGAP2:c.479C>T
C
PGAP2|c.479
[u'NP_001243169.1']
NP_001243169.1:c.479C>T
NP_001243169.1:c.479C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MLH1:c.27C>A
C
MLH1|c.27
[u'NM_000249.2']
NM_000249.2:c.27C>A
NM_000249.2:c.27C>A
37035065
MLH1:c.85G>T
G
MLH1|c.85
[u'NM_000249.2']
NM_000249.2:c.85G>T
NM_000249.2:c.85G>T
37035123
MLH1:c.27C>A
C
MLH1|c.27
[u'NM_000249.2']
NM_000249.2:c.27C>A
NM_000249.2:c.27C>A
37035065
MLH1:c.85G>T
G
MLH1|c.85
[u'NM_000249.2']
NM_000249.2:c.85G>T
NM_000249.2:c.85G>T
37035123
SERPING1:c.1459C>T
C
SERPING1|c.1459
[u'NG_009625']
NG_009625:c.1459C>T
NG_009625:c.1459C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SERPING1:c.1174C>T
C
SERPING1|c.1174
[u'NG_009625']
NG_009625:c.1174C>T
NG_009625:c.1174C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
LDLR:c.2140+5G>A
G
LDLR|c.2140+5
[u'NM_000527']
NM_000527:c.2140+5G>A
NM_000527:c.2140+5G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SIX6:c.2015T>C
T
SIX6|c.2015
[u'NC_007308']
NC_007308:c.2015T>C
NC_007308:c.2015T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GRM1:c.2660+2T>G
T
GRM1|c.2660+2
[u'NM_000838.3']
NM_000838.3:c.2660+2T>G
NM_000838.3:c.2660+2T>G
146720837
PLAC8:c.925G>C
G
PLAC8|c.925
[u'NG_000007.3']
NG_000007.3:c.925G>C
NG_000007.3:c.925G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PLAC8:c.92G>T
G
PLAC8|c.92
[u'NG_000007.3']
NG_000007.3:c.92G>T
NG_000007.3:c.92G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PLAC8:c.47G>A
G
PLAC8|c.47
[u'NG_000007.3']
NG_000007.3:c.47G>A
NG_000007.3:c.47G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PLAC8:c.93G>C
G
PLAC8|c.93
[u'NG_000007.3']
NG_000007.3:c.93G>C
NG_000007.3:c.93G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MTHFR:c.677C>T
C
MTHFR|c.677
[u'NM_005957.4']
NM_005957.4:c.677C>T
NM_005957.4:c.677C>T
11856366
MTHFR:c.665C>T
C
MTHFR|c.665
[u'NM_005957.4']
NM_005957.4:c.665C>T
NM_005957.4:c.665C>T
11856378
MTHFR:c.677C>T
C
MTHFR|c.677
[u'NM_005957.4']
NM_005957.4:c.677C>T
NM_005957.4:c.677C>T
11856366
MTHFR:c.665C>T
C
MTHFR|c.665
[u'NM_005957.4']
NM_005957.4:c.665C>T
NM_005957.4:c.665C>T
11856378
HBB:c.35A>G
A
HBB|c.35
[u'NG_000007.3']
NG_000007.3:c.35A>G
NG_000007.3:c.35A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HBB:c.142G>A
G
HBB|c.142
[u'NG_000007.3']
NG_000007.3:c.142G>A
NG_000007.3:c.142G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HBB:c.182G>A
G
HBB|c.182
[u'NG_000007.3']
NG_000007.3:c.182G>A
NG_000007.3:c.182G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
LARS2:c.899C>T
C
LARS2|c.899
[u'NM_015340.3']
NM_015340.3:c.899C>T
NM_015340.3:c.899C>T
45518000
LARS2:c.1912G>A
G
LARS2|c.1912
[u'NM_015340.3']
NM_015340.3:c.1912G>A
NM_015340.3:c.1912G>A
45557636
KARS:c.1312C>T
C
KARS|c.1312
[u'NM_005548.2']
NM_005548.2:c.1312C>T
NM_005548.2:c.1312C>T
75665092
KARS:c.1573G>A
G
KARS|c.1573
[u'NM_005548.2']
NM_005548.2:c.1573G>A
NM_005548.2:c.1573G>A
75662589
PROS1:c.1907A>G
A
PROS1|c.1907
[u'NM_000313.3']
NM_000313.3:c.1907A>G
NM_000313.3:c.1907A>G
93593213
PCBD1:c.449A>G
A
PCBD1|c.449
[u'NM_031427.3']
NM_031427.3:c.449A>G
NM_031427.3:c.449A>G
74156135
ASNS:c.866G>C
G
ASNS|c.866
[u'NM_183356.3']
NM_183356.3:c.866G>C
NM_183356.3:c.866G>C
97487627
ASNS:c.1010C>T
C
ASNS|c.1010
[u'NM_183356.3']
NM_183356.3:c.1010C>T
NM_183356.3:c.1010C>T
97486022
EDA:c.866G>T
G
EDA|c.866
[u'NM_001399.4']
NM_001399.4:c.866G>T
NM_001399.4:c.866G>T
69253320
EDA:c.1135T>G
T
EDA|c.1135
[u'NM_001399.4']
NM_001399.4:c.1135T>G
NM_001399.4:c.1135T>G
69255418
PRPS1:c.337G>T
G
PRPS1|c.337
[u'NM_002764.3']
NM_002764.3:c.337G>T
NM_002764.3:c.337G>T
106884162
PRPS1:c.343A>G
A
PRPS1|c.343
[u'NM_002764.3']
NM_002764.3:c.343A>G
NM_002764.3:c.343A>G
106884168
PRPS1:c.925G>T
G
PRPS1|c.925
[u'NM_002764.3']
NM_002764.3:c.925G>T
NM_002764.3:c.925G>T
106893230
PRPS1:c.343A>G
A
PRPS1|c.343
[u'NM_002764.3']
NM_002764.3:c.343A>G
NM_002764.3:c.343A>G
106884168
PRPS1:c.925G>T
G
PRPS1|c.925
[u'NM_002764.3']
NM_002764.3:c.925G>T
NM_002764.3:c.925G>T
106893230
VHL:c.463+1G>T
G
VHL|c.463+1
[u'NM_000551.2']
NM_000551.2:c.463+1G>T
NM_000551.2:c.463+1G>T
10188321
VHL:c.233A>G
A
VHL|c.233
[u'NM_000551.2']
NM_000551.2:c.233A>G
NM_000551.2:c.233A>G
10183764
VHL:c.239G>T
G
VHL|c.239
[u'NM_000551.2']
NM_000551.2:c.239G>T
NM_000551.2:c.239G>T
10183770
VHL:c.319C>G
C
VHL|c.319
[u'NM_000551.2']
NM_000551.2:c.319C>G
NM_000551.2:c.319C>G
10183850
VHL:c.481C>T
C
VHL|c.481
[u'NM_000551.2']
NM_000551.2:c.481C>T
NM_000551.2:c.481C>T
10191488
VHL:c.482G>A
G
VHL|c.482
[u'NM_000551.2']
NM_000551.2:c.482G>A
NM_000551.2:c.482G>A
10191489
VHL:c.499C>T
C
VHL|c.499
[u'NM_000551.2']
NM_000551.2:c.499C>T
NM_000551.2:c.499C>T
10191506
FH:c.1413A>G
A
FH|c.1413
[u'NM_001195798.1']
NM_001195798.1:c.1413A>G
NM_001195798.1:c.1413A>G
11224265
KIDINS220:c.92+5G>C
G
KIDINS220|c.92+5
[u'NG_000007.3']
NG_000007.3:c.92+5G>C
NG_000007.3:c.92+5G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
KIDINS220:c.138C>G
C
KIDINS220|c.138
[u'NG_000007.3']
NG_000007.3:c.138C>G
NG_000007.3:c.138C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
KIDINS220:c.140C>T
C
KIDINS220|c.140
[u'NG_000007.3']
NG_000007.3:c.140C>T
NG_000007.3:c.140C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SMARCA4:c.3277C>T
C
SMARCA4|c.3277
[u'NG_011556.1']
NG_011556.1:c.3277C>T
NG_011556.1:c.3277C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SMARCA4:c.3760G>T
G
SMARCA4|c.3760
[u'NG_011556.1']
NG_011556.1:c.3760G>T
NG_011556.1:c.3760G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PSEN1:c.839A>C
A
PSEN1|c.839
[u'NM_000021.3']
NM_000021.3:c.839A>C
NM_000021.3:c.839A>C
73664808
CACNA1A:c.4110T>G
T
CACNA1A|c.4110
[u'NM_000068.3']
NM_000068.3:c.4110T>G
NM_000068.3:c.4110T>G
13372416
GPAT4:g.152G>C
G
GPAT4|g.152
[u'NC_007328.3']
NC_007328.3:g.152G>C
NC_007328.3:g.152G>C
DATA RETURNED: None
TEXT RETURNED: null
None
GPAT4:c.8124G>A
G
GPAT4|c.8124
[u'NC_007328.3']
NC_007328.3:c.8124G>A
NC_007328.3:c.8124G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GPAT4:c.9263C>G
C
GPAT4|c.9263
[u'NC_007328.3']
NC_007328.3:c.9263C>G
NC_007328.3:c.9263C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GPAT4:c.16436G>A
G
GPAT4|c.16436
[u'NC_007328.3']
NC_007328.3:c.16436G>A
NC_007328.3:c.16436G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GPAT4:c.9263C>G
C
GPAT4|c.9263
[u'NC_007328.3']
NC_007328.3:c.9263C>G
NC_007328.3:c.9263C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GPAT4:c.9263C>G
C
GPAT4|c.9263
[u'NC_007328.3']
NC_007328.3:c.9263C>G
NC_007328.3:c.9263C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SSB:c.552-2A>G
A
SSB|c.552-2
[u'NM_000194.2']
NM_000194.2:c.552-2A>G
NM_000194.2:c.552-2A>G
133632655
mtdna:m.13094T>C
T
mtdna|m.13094
[u'NC_012920.1']
NC_012920.1:m.13094T>C
NC_012920.1:m.13094T>C
Could not parse: ["NC_012920.1(COX2_v001):c.*4825T>C", "NC_012920.1(TRNK_v001):n.*4730T>C", "NC_012920.1(ATP8_v001):c.*4522T>C", "NC_012920.1(ATP6_v001):c.*3887T>C", "NC_012920.1(COX3_v001):c.*3104T>C", "NC_012920.1(TRNG_v001):n.*3036T>C", "NC_012920.1(ND3_v001):c.*2690T>C", "NC_012920.1(TRNR_v001):n.*2625T>C", "NC_012920.1(ND4L_v001):c.*2328T>C", "NC_012920.1(ND4_v001):c.*957T>C", "NC_012920.1(TRNH_v001):n.*888T>C", "NC_012920.1(TRNS2_v001):n.*829T>C", "NC_012920.1(TRNL2_v001):n.*758T>C", "NC_012920.1(ND5_v001):c.758T>C", "NC_012920.1(ND6_v001):c.*1055A>G", "NC_012920.1(TRNE_v001):n.*1580A>G", "NC_012920.1(CYTB_v001):c.-1653T>C", "NC_012920.1(TRNT_v001):n.-2794T>C", "NC_012920.1(TRNP_v001):n.*2862A>G"]
None
NDUFV1:c.1162+4A>C
A
NDUFV1|c.1162+4
[u'NM_007103.3']
NM_007103.3:c.1162+4A>C
NM_007103.3:c.1162+4A>C
67379453
NDUFV1:c.640G>A
G
NDUFV1|c.640
[u'NM_007103.3']
NM_007103.3:c.640G>A
NM_007103.3:c.640G>A
67377981
GALNT12:c.907G>A
G
GALNT12|c.907
[u'NM_024642.4']
NM_024642.4:c.907G>A
NM_024642.4:c.907G>A
101594229
GALNT12:c.907G>A
G
GALNT12|c.907
[u'NM_024642.4']
NM_024642.4:c.907G>A
NM_024642.4:c.907G>A
101594229
GALNT12:c.907G>A
G
GALNT12|c.907
[u'NM_024642.4']
NM_024642.4:c.907G>A
NM_024642.4:c.907G>A
101594229
SPARC:c.497G>A
G
SPARC|c.497
[u'NM_003118.3']
NM_003118.3:c.497G>A
NM_003118.3:c.497G>A
151047116
SPARC:c.787G>A
G
SPARC|c.787
[u'NM_003118.3']
NM_003118.3:c.787G>A
NM_003118.3:c.787G>A
151043744
COG6:c.1167-24A>G
A
COG6|c.1167-24
[u'NM_020751.2']
NM_020751.2:c.1167-24A>G
NM_020751.2:c.1167-24A>G
40273614
OCA2:g.1124477G>A
G
OCA2|g.1124477
[u'NW_001494061']
NW_001494061:g.1124477G>A
NW_001494061:g.1124477G>A
DATA RETURNED: None
TEXT RETURNED: null
None
OCA2:g.1118561T>C
T
OCA2|g.1118561
[u'NW_001494061']
NW_001494061:g.1118561T>C
NW_001494061:g.1118561T>C
DATA RETURNED: None
TEXT RETURNED: null
None
AMBN:g.13081786G>A
G
AMBN|g.13081786
[u'NM_014208.3']
NM_014208.3:g.13081786G>A
NM_014208.3:g.13081786G>A
DATA RETURNED: None
TEXT RETURNED: null
None
AMBN:c.727G>A
G
AMBN|c.727
[u'NM_014208.3']
NM_014208.3:c.727G>A
NM_014208.3:c.727G>A
88534065
PITX2:g.18117T>C
T
PITX2|g.18117
[u'AC_000163']
AC_000163:g.18117T>C
AC_000163:g.18117T>C
DATA RETURNED: None
TEXT RETURNED: null
None
PITX2:g.18161C>G
C
PITX2|g.18161
[u'AC_000163']
AC_000163:g.18161C>G
AC_000163:g.18161C>G
DATA RETURNED: None
TEXT RETURNED: null
None
PITX2:g.18322C>A
C
PITX2|g.18322
[u'AC_000163']
AC_000163:g.18322C>A
AC_000163:g.18322C>A
DATA RETURNED: None
TEXT RETURNED: null
None
PITX2:g.18353T>C
T
PITX2|g.18353
[u'AC_000163']
AC_000163:g.18353T>C
AC_000163:g.18353T>C
DATA RETURNED: None
TEXT RETURNED: null
None
PITX2:c.79C>A
C
PITX2|c.79
[u'AC_000163']
AC_000163:c.79C>A
AC_000163:c.79C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PITX2:c.110T>C
T
PITX2|c.110
[u'AC_000163']
AC_000163:c.110T>C
AC_000163:c.110T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HSF4:c.1213C>T
C
HSF4|c.1213
[u'NM_001040667']
NM_001040667:c.1213C>T
NM_001040667:c.1213C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PRDM16:g.577G>T
G
PRDM16|g.577
[u'NC_007314.3']
NC_007314.3:g.577G>T
NC_007314.3:g.577G>T
DATA RETURNED: None
TEXT RETURNED: null
None
PRDM16:c.614T>C
T
PRDM16|c.614
[u'NC_007314.3']
NC_007314.3:c.614T>C
NC_007314.3:c.614T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PRDM16:c.212237T>C
T
PRDM16|c.212237
[u'NC_007314.3']
NC_007314.3:c.212237T>C
NC_007314.3:c.212237T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
LMNA:c.1774G>A
G
LMNA|c.1774
[u'NM_170707.3']
NM_170707.3:c.1774G>A
NM_170707.3:c.1774G>A
156108354
EDAR:c.361C>T
C
EDAR|c.361
[u'NM_080738']
NM_080738:c.361C>T
NM_080738:c.361C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PSMB5:g.417C>G
C
PSMB5|g.417
[u'NM_000546.5']
NM_000546.5:g.417C>G
NM_000546.5:g.417C>G
DATA RETURNED: None
TEXT RETURNED: null
None
CD55:g.12345T>C
T
CD55|g.12345
[u'NC_007300']
NC_007300:g.12345T>C
NC_007300:g.12345T>C
DATA RETURNED: None
TEXT RETURNED: null
None
MTHFR:c.677C>T
C
MTHFR|c.677
[u'NM_005957']
NM_005957:c.677C>T
NM_005957:c.677C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MTHFR:c.677C>T
C
MTHFR|c.677
[u'NM_005957']
NM_005957:c.677C>T
NM_005957:c.677C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
Records: 30000
GJB1:c.459C>T
C
GJB1|c.459
[u'NM_000166']
NM_000166:c.459C>T
NM_000166:c.459C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GJB1:c.713G>A
G
GJB1|c.713
[u'NM_000166']
NM_000166:c.713G>A
NM_000166:c.713G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GJB1:c.459C>T
C
GJB1|c.459
[u'NM_000166']
NM_000166:c.459C>T
NM_000166:c.459C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GJB1:c.459C>T
C
GJB1|c.459
[u'NM_000166']
NM_000166:c.459C>T
NM_000166:c.459C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HFE:c.845G>A
G
HFE|c.845
[u'NC_000006.10']
NC_000006.10:c.845G>A
NC_000006.10:c.845G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HFE:c.845G>A
G
HFE|c.845
[u'NC_000006.10']
NC_000006.10:c.845G>A
NC_000006.10:c.845G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HFE:c.187C>G
C
HFE|c.187
[u'NC_000006.10']
NC_000006.10:c.187C>G
NC_000006.10:c.187C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HFE:c.128G>A
G
HFE|c.128
[u'NC_000006.10']
NC_000006.10:c.128G>A
NC_000006.10:c.128G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HFE:c.187C>G
C
HFE|c.187
[u'NC_000006.10']
NC_000006.10:c.187C>G
NC_000006.10:c.187C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HFE:c.128G>A
G
HFE|c.128
[u'NC_000006.10']
NC_000006.10:c.128G>A
NC_000006.10:c.128G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HFE:c.187C>G
C
HFE|c.187
[u'NC_000006.10']
NC_000006.10:c.187C>G
NC_000006.10:c.187C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
HFE:c.845G>A
G
HFE|c.845
[u'NC_000006.10']
NC_000006.10:c.845G>A
NC_000006.10:c.845G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PTEN:c.545T>C
T
PTEN|c.545
[u'NM_000314.4']
NM_000314.4:c.545T>C
NM_000314.4:c.545T>C
89711927
SACS:c.3491T>A
T
SACS|c.3491
[u'NM_014363.3']
NM_014363.3:c.3491T>A
NM_014363.3:c.3491T>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
ALG9:c.1173+2T>A
T
ALG9|c.1173+2
[u'NM_024740.2']
NM_024740.2:c.1173+2T>A
NM_024740.2:c.1173+2T>A
111711377
{'end': 111711376, 'tr': 2, 'allele_string': [u'T', u'A'], 'start': 111711376, 'chr': u'11', 'strand': -1}
A rare lethal autosomal recessive syndrome with skeletal dysplasia, polycystic kidneys and multiple malformations was first described by Gillessen-Kaesbach et al and subsequently by Nishimura et al. The skeletal features uniformly comprise a round pelvis, mesomelic shortening of the upper limbs and defective ossification of the cervical spine. We studied two unrelated families including three affected fetuses with Gillessen-Kaesbach-Nishimura syndrome using whole-exome and Sanger sequencing, comparative genome hybridization and homozygosity mapping. All affected patients were shown to have a novel homozygous splice variant NM_024740.2: c.1173+2T>A in the ALG9 gene, encoding alpha-1,2-mannosyltransferase, involved in the formation of the lipid-linked oligosaccharide precursor of N-glycosylation. RNA analysis demonstrated skipping of exon 10, leading to shorter RNA. Mass spectrometric analysis showed an increase in monoglycosylated transferrin as compared with control tissues, confirming that this is a congenital disorder of glycosylation (CDG). Only three liveborn children with ALG9-CDG have been previously reported, all with missense variants. All three suffered from intellectual disability, muscular hypotonia, microcephaly and renal cysts, but none had skeletal dysplasia. Our study shows that some pathogenic variants in ALG9 can present as a lethal skeletal dysplasia with visceral malformations as the most severe phenotype. The skeletal features overlap with that previously reported for ALG3- and ALG12-CDG, suggesting that this subset of glycosylation disorders constitutes a new diagnostic group of skeletal dysplasias.
SERPINE1:g.566G>A
G
SERPINE1|g.566
[u'NM_213910']
NM_213910:g.566G>A
NM_213910:g.566G>A
DATA RETURNED: None
TEXT RETURNED: null
None
SERPINE1:c.612A>G
A
SERPINE1|c.612
[u'NM_213910']
NM_213910:c.612A>G
NM_213910:c.612A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
mtdna:m.6267G>A
G
mtdna|m.6267
[u'NP_536845.1']
NP_536845.1:m.6267G>A
NP_536845.1:m.6267G>A
DATA RETURNED: None
TEXT RETURNED: null
None
mtdna:m.6267G>A
G
mtdna|m.6267
[u'NP_536845.1']
NP_536845.1:m.6267G>A
NP_536845.1:m.6267G>A
DATA RETURNED: None
TEXT RETURNED: null
None
mtdna:m.6267G>A
G
mtdna|m.6267
[u'NP_536845.1']
NP_536845.1:m.6267G>A
NP_536845.1:m.6267G>A
DATA RETURNED: None
TEXT RETURNED: null
None
mtdna:m.6267G>A
G
mtdna|m.6267
[u'NP_536845.1']
NP_536845.1:m.6267G>A
NP_536845.1:m.6267G>A
DATA RETURNED: None
TEXT RETURNED: null
None
mtdna:m.6267G>A
G
mtdna|m.6267
[u'NP_536845.1']
NP_536845.1:m.6267G>A
NP_536845.1:m.6267G>A
DATA RETURNED: None
TEXT RETURNED: null
None
MALT1:c.1019-2A>G
A
MALT1|c.1019-2
[u'NM_006785.3']
NM_006785.3:c.1019-2A>G
NM_006785.3:c.1019-2A>G
56390278
CFTR:c.3718-2477C>T
C
CFTR|c.3718-2477
[u'NM_000492.2']
NM_000492.2:c.3718-2477C>T
NM_000492.2:c.3718-2477C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CFTR:c.1558G>T
G
CFTR|c.1558
[u'NM_000492.2']
NM_000492.2:c.1558G>T
NM_000492.2:c.1558G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CFTR:c.1364C>A
C
CFTR|c.1364
[u'NM_000492.2']
NM_000492.2:c.1364C>A
NM_000492.2:c.1364C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CFTR:c.1040G>C
G
CFTR|c.1040
[u'NM_000492.2']
NM_000492.2:c.1040G>C
NM_000492.2:c.1040G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CFTR:c.3846G>A
G
CFTR|c.3846
[u'NM_000492.2']
NM_000492.2:c.3846G>A
NM_000492.2:c.3846G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CFTR:c.350G>A
G
CFTR|c.350
[u'NM_000492.2']
NM_000492.2:c.350G>A
NM_000492.2:c.350G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CFTR:c.254G>A
G
CFTR|c.254
[u'NM_000492.2']
NM_000492.2:c.254G>A
NM_000492.2:c.254G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CFTR:c.1G>T
G
CFTR|c.1
[u'NM_000492.2']
NM_000492.2:c.1G>T
NM_000492.2:c.1G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CFTR:c.1G>T
G
CFTR|c.1
[u'NM_000492.2']
NM_000492.2:c.1G>T
NM_000492.2:c.1G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CFTR:c.5G>A
G
CFTR|c.5
[u'NM_000492.2']
NM_000492.2:c.5G>A
NM_000492.2:c.5G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CFTR:c.5G>A
G
CFTR|c.5
[u'NM_000492.2']
NM_000492.2:c.5G>A
NM_000492.2:c.5G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
NR3C2:c.1A>T
A
NR3C2|c.1
[u'NM_006517']
NM_006517:c.1A>T
NM_006517:c.1A>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
NR3C2:c.1673G>A
G
NR3C2|c.1673
[u'NM_006517']
NM_006517:c.1673G>A
NM_006517:c.1673G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
NR3C2:c.1673G>A
G
NR3C2|c.1673
[u'NM_006517']
NM_006517:c.1673G>A
NM_006517:c.1673G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
NR3C2:c.1A>T
A
NR3C2|c.1
[u'NM_006517']
NM_006517:c.1A>T
NM_006517:c.1A>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
NR3C2:c.1A>T
A
NR3C2|c.1
[u'NM_006517']
NM_006517:c.1A>T
NM_006517:c.1A>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MCF2L:c.2066A>G
A
MCF2L|c.2066
[u'NM_001112732.1']
NM_001112732.1:c.2066A>G
NM_001112732.1:c.2066A>G
113736760
{'end': 113739210, 'tr': 1, 'allele_string': [u'A', u'G'], 'start': 113739210, 'chr': u'13', 'strand': 1}
Cardiovascular disease (CVD) is a major cause of death in Western societies. CVD risk is largely genetically determined. The molecular pathology is, however, not elucidated in a large number of families suffering from CVD. We applied exclusion linkage analysis and next-generation sequencing to elucidate the molecular defect underlying premature CVD in a small pedigree, comprising two generations of which six members suffered from premature CVD. A total of three variants showed co-segregation with the disease status in the family. Two of these variants were excluded from further analysis based on the prevalence in replication cohorts, whereas a non-synonymous variant in MCF.2 Cell Line Derived Transforming Sequence-like protein (MCF2L, c.2066A>G; p.(Asp689Gly); NM_001112732.1), located in the DH domain, was only present in the studied family. MCF2L is a guanine exchange factor that potentially links pathways that signal through Rac1 and RhoA. Indeed, in HeLa cells, MCF2L689Gly failed to activate Rac1 as well as RhoA, resulting in impaired stress fiber formation. Moreover, MCF2L protein was found in human atherosclerotic lesions but not in healthy tissue segments. In conclusion, a rare functional variant in MCF2L, leading to impaired DH function, was identified in a small pedigree with premature CVD. The presence of MCF2L in human atherosclerotic plaque specimen lends further support to its potential role in atherosclerosis.
MAOA:g.80340C>T
C
MAOA|g.80340
[u'NC_007331.3']
NC_007331.3:g.80340C>T
NC_007331.3:g.80340C>T
DATA RETURNED: None
TEXT RETURNED: null
None
FGFR2:c.890G>C
G
FGFR2|c.890
[u'NM_000141']
NM_000141:c.890G>C
NM_000141:c.890G>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SH2D1A:c.47G>A
G
SH2D1A|c.47
[u'NP_002342']
NP_002342:c.47G>A
NP_002342:c.47G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GPR143:g.25288G>A
G
GPR143|g.25288
[u'NC_000023.8']
NC_000023.8:g.25288G>A
NC_000023.8:g.25288G>A
DATA RETURNED: None
TEXT RETURNED: null
None
CS:c.34G>A
G
CS|c.34
[u'NM_005343.2']
NM_005343.2:c.34G>A
NM_005343.2:c.34G>A
534289
{'end': 56693952, 'tr': 3, 'allele_string': [u'G', u'A'], 'start': 56693952, 'chr': u'12', 'strand': -1}
Costello syndrome (CS) is a rare congenital condition caused by heterozygous de novo missense mutations affecting the codon for glycine 12 or 13 of the HRAS gene. We have identified 39 CS patients harboring the p.Gly12Ser mutation (NM_005343.2:c.34 G > A), two patients with c.35G > C mutations resulting in p.Gly12Ala substitutions, and one patient carrying the p.Gly13Cys substitution (c.37G > A). We analyzed the region flanking the mutated sites in 42 probands and 59 parents, and used four polymorphic markers to trace the parental origin of the germline mutations: one highly polymorphic hexanucleotide (GGGCCT) repeat region, defining three alleles with different numbers of repeat units (two, three, or four), and three SNPs. One of the SNPs, rs12628 (c.81T > C), was found in strong linkage disequilibrium with the hexanucleotide repeat region. Out of a total of 24 probands with polymorphic markers, 16 informative families were tested and the paternal origin of the germline mutation was found in 14 CS probands; a distribution that is neither consistent with an equal likelihood of mutations arising in either parent (P = 0.0018), nor with exclusive paternal origin.
CS:c.35G>C
G
CS|c.35
[u'NM_005343.2']
NM_005343.2:c.35G>C
NM_005343.2:c.35G>C
534288
{'end': 56693951, 'tr': 3, 'allele_string': [u'G', u'C'], 'start': 56693951, 'chr': u'12', 'strand': -1}
Costello syndrome (CS) is a rare congenital condition caused by heterozygous de novo missense mutations affecting the codon for glycine 12 or 13 of the HRAS gene. We have identified 39 CS patients harboring the p.Gly12Ser mutation (NM_005343.2:c.34 G > A), two patients with c.35G > C mutations resulting in p.Gly12Ala substitutions, and one patient carrying the p.Gly13Cys substitution (c.37G > A). We analyzed the region flanking the mutated sites in 42 probands and 59 parents, and used four polymorphic markers to trace the parental origin of the germline mutations: one highly polymorphic hexanucleotide (GGGCCT) repeat region, defining three alleles with different numbers of repeat units (two, three, or four), and three SNPs. One of the SNPs, rs12628 (c.81T > C), was found in strong linkage disequilibrium with the hexanucleotide repeat region. Out of a total of 24 probands with polymorphic markers, 16 informative families were tested and the paternal origin of the germline mutation was found in 14 CS probands; a distribution that is neither consistent with an equal likelihood of mutations arising in either parent (P = 0.0018), nor with exclusive paternal origin.
CS:c.37G>A
G
CS|c.37
[u'NM_005343.2']
NM_005343.2:c.37G>A
NM_005343.2:c.37G>A
534286
CS:c.81T>C
T
CS|c.81
[u'NM_005343.2']
NM_005343.2:c.81T>C
NM_005343.2:c.81T>C
534242
{'end': 56680391, 'tr': 2, 'allele_string': [u'T', u'C'], 'start': 56680391, 'chr': u'12', 'strand': -1}
Costello syndrome (CS) is a rare congenital condition caused by heterozygous de novo missense mutations affecting the codon for glycine 12 or 13 of the HRAS gene. We have identified 39 CS patients harboring the p.Gly12Ser mutation (NM_005343.2:c.34 G > A), two patients with c.35G > C mutations resulting in p.Gly12Ala substitutions, and one patient carrying the p.Gly13Cys substitution (c.37G > A). We analyzed the region flanking the mutated sites in 42 probands and 59 parents, and used four polymorphic markers to trace the parental origin of the germline mutations: one highly polymorphic hexanucleotide (GGGCCT) repeat region, defining three alleles with different numbers of repeat units (two, three, or four), and three SNPs. One of the SNPs, rs12628 (c.81T > C), was found in strong linkage disequilibrium with the hexanucleotide repeat region. Out of a total of 24 probands with polymorphic markers, 16 informative families were tested and the paternal origin of the germline mutation was found in 14 CS probands; a distribution that is neither consistent with an equal likelihood of mutations arising in either parent (P = 0.0018), nor with exclusive paternal origin.
SEPT9:c.278C>T
C
SEPT9|c.278
[u'NM_006640.3']
NM_006640.3:c.278C>T
NM_006640.3:c.278C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
SEPT9:c.262C>T
C
SEPT9|c.262
[u'NM_006640.3']
NM_006640.3:c.262C>T
NM_006640.3:c.262C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PCYT1A:c.12A>G
A
PCYT1A|c.12
[u'NM_001046020']
NM_001046020:c.12A>G
NM_001046020:c.12A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PCYT1A:c.276C>T
C
PCYT1A|c.276
[u'NM_001046020']
NM_001046020:c.276C>T
NM_001046020:c.276C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PCYT1A:c.321A>G
A
PCYT1A|c.321
[u'NM_001046020']
NM_001046020:c.321A>G
NM_001046020:c.321A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PCYT1A:c.396C>T
C
PCYT1A|c.396
[u'NM_001046020']
NM_001046020:c.396C>T
NM_001046020:c.396C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PCYT1A:c.12A>G
A
PCYT1A|c.12
[u'NM_001046020']
NM_001046020:c.12A>G
NM_001046020:c.12A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PCYT1A:c.321A>G
A
PCYT1A|c.321
[u'NM_001046020']
NM_001046020:c.321A>G
NM_001046020:c.321A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PCYT1A:c.396C>T
C
PCYT1A|c.396
[u'NM_001046020']
NM_001046020:c.396C>T
NM_001046020:c.396C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PCYT1A:c.276C>T
C
PCYT1A|c.276
[u'NM_001046020']
NM_001046020:c.276C>T
NM_001046020:c.276C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PCYT1A:c.276C>T
C
PCYT1A|c.276
[u'NM_001046020']
NM_001046020:c.276C>T
NM_001046020:c.276C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
PCYT1A:c.276C>T
C
PCYT1A|c.276
[u'NM_001046020']
NM_001046020:c.276C>T
NM_001046020:c.276C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GHRHR:g.5203C>T
C
GHRHR|g.5203
[u'NC_007302']
NC_007302:g.5203C>T
NC_007302:g.5203C>T
DATA RETURNED: None
TEXT RETURNED: null
None
GHRHR:c.7307C>G
C
GHRHR|c.7307
[u'NC_007302']
NC_007302:c.7307C>G
NC_007302:c.7307C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GHRHR:c.9583G>A
G
GHRHR|c.9583
[u'NC_007302']
NC_007302:c.9583G>A
NC_007302:c.9583G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GHRHR:c.9668A>C
A
GHRHR|c.9668
[u'NC_007302']
NC_007302:c.9668A>C
NC_007302:c.9668A>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GHRHR:c.9583G>A
G
GHRHR|c.9583
[u'NC_007302']
NC_007302:c.9583G>A
NC_007302:c.9583G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GHRHR:c.9668A>C
A
GHRHR|c.9668
[u'NC_007302']
NC_007302:c.9668A>C
NC_007302:c.9668A>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CHD4:c.3380G>A
G
CHD4|c.3380
[u'NM_001273.3']
NM_001273.3:c.3380G>A
NM_001273.3:c.3380G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CHD4:c.3443G>T
G
CHD4|c.3443
[u'NM_001273.3']
NM_001273.3:c.3443G>T
NM_001273.3:c.3443G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CHD4:c.3518G>T
G
CHD4|c.3518
[u'NM_001273.3']
NM_001273.3:c.3518G>T
NM_001273.3:c.3518G>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CHD4:c.3008G>A
G
CHD4|c.3008
[u'NM_001273.3']
NM_001273.3:c.3008G>A
NM_001273.3:c.3008G>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
NRP2:c.1938-21T>C
T
NRP2|c.1938-21
[u'XM_371590']
XM_371590:c.1938-21T>C
XM_371590:c.1938-21T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
NRP2:c.1938-21T>C
T
NRP2|c.1938-21
[u'XM_371590']
XM_371590:c.1938-21T>C
XM_371590:c.1938-21T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
IDH1:c.933-28C>T
C
IDH1|c.933-28
[u'XM_371590']
XM_371590:c.933-28C>T
XM_371590:c.933-28C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
Records: 40000
ALOXE3:c.814C>T
C
ALOXE3|c.814
[u'NM_001165960.1']
NM_001165960.1:c.814C>T
NM_001165960.1:c.814C>T
8018941
CTSD:g.569834T>C
T
CTSD|g.569834
[u'NT_009237.17']
NT_009237.17:g.569834T>C
NT_009237.17:g.569834T>C
DATA RETURNED: None
TEXT RETURNED: null
None
MGMT:c.56C>T
C
MGMT|c.56
[u'NM_002412.2']
NM_002412.2:c.56C>T
NM_002412.2:c.56C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MGMT:c.56C>T
C
MGMT|c.56
[u'NM_002412.2']
NM_002412.2:c.56C>T
NM_002412.2:c.56C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
MGMT:c.56C>T
C
MGMT|c.56
[u'NM_002412.2']
NM_002412.2:c.56C>T
NM_002412.2:c.56C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
GIF:g.68A>G
A
GIF|g.68
[u'NM_005142']
NM_005142:g.68A>G
NM_005142:g.68A>G
DATA RETURNED: None
TEXT RETURNED: null
None
LMLN:g.67C>G
C
LMLN|g.67
[u'NM_005142']
NM_005142:g.67C>G
NM_005142:g.67C>G
DATA RETURNED: None
TEXT RETURNED: null
None
GIF:g.68A>G
A
GIF|g.68
[u'NM_005142']
NM_005142:g.68A>G
NM_005142:g.68A>G
DATA RETURNED: None
TEXT RETURNED: null
None
GIF:g.68A>G
A
GIF|g.68
[u'NM_005142']
NM_005142:g.68A>G
NM_005142:g.68A>G
DATA RETURNED: None
TEXT RETURNED: null
None
GIF:g.68A>G
A
GIF|g.68
[u'NM_005142']
NM_005142:g.68A>G
NM_005142:g.68A>G
DATA RETURNED: None
TEXT RETURNED: null
None
LMLN:g.67C>G
C
LMLN|g.67
[u'NM_005142']
NM_005142:g.67C>G
NM_005142:g.67C>G
DATA RETURNED: None
TEXT RETURNED: null
None
GIF:g.68A>G
A
GIF|g.68
[u'NM_005142']
NM_005142:g.68A>G
NM_005142:g.68A>G
DATA RETURNED: None
TEXT RETURNED: null
None
GIF:g.68A>G
A
GIF|g.68
[u'NM_005142']
NM_005142:g.68A>G
NM_005142:g.68A>G
DATA RETURNED: None
TEXT RETURNED: null
None
CYP3A5:c.13108T>C
T
CYP3A5|c.13108
[u'NG_000004.2']
NG_000004.2:c.13108T>C
NG_000004.2:c.13108T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.16025A>G
A
CYP3A5|c.16025
[u'NG_000004.2']
NG_000004.2:c.16025A>G
NG_000004.2:c.16025A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.16903A>G
A
CYP3A5|c.16903
[u'NG_000004.2']
NG_000004.2:c.16903A>G
NG_000004.2:c.16903A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.16993C>G
C
CYP3A5|c.16993
[u'NG_000004.2']
NG_000004.2:c.16993C>G
NG_000004.2:c.16993C>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.27448C>A
C
CYP3A5|c.27448
[u'NG_000004.2']
NG_000004.2:c.27448C>A
NG_000004.2:c.27448C>A
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.29782A>G
A
CYP3A5|c.29782
[u'NG_000004.2']
NG_000004.2:c.29782A>G
NG_000004.2:c.29782A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.31551T>C
T
CYP3A5|c.31551
[u'NG_000004.2']
NG_000004.2:c.31551T>C
NG_000004.2:c.31551T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.6986A>G
A
CYP3A5|c.6986
[u'NG_000004.2']
NG_000004.2:c.6986A>G
NG_000004.2:c.6986A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.29782A>G
A
CYP3A5|c.29782
[u'NG_000004.2']
NG_000004.2:c.29782A>G
NG_000004.2:c.29782A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.31551T>C
T
CYP3A5|c.31551
[u'NG_000004.2']
NG_000004.2:c.31551T>C
NG_000004.2:c.31551T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.12952T>C
T
CYP3A5|c.12952
[u'NG_000004.2']
NG_000004.2:c.12952T>C
NG_000004.2:c.12952T>C
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.6986A>G
A
CYP3A5|c.6986
[u'NG_000004.2']
NG_000004.2:c.6986A>G
NG_000004.2:c.6986A>G
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
CYP3A5:c.31611C>T
C
CYP3A5|c.31611
[u'NG_000004.2']
NG_000004.2:c.31611C>T
NG_000004.2:c.31611C>T
DATA RETURNED: [None]
TEXT RETURNED: [null]
None
Created problematic_abstracts.json
{
    "TRANSCRIPT_COUNTER_6": 194, 
    "TRANSCRIPT_COUNTER_7": 103, 
    "TRANSCRIPT_COUNTER_4": 955, 
    "TRANSCRIPT_COUNTER_5": 255, 
    "TRANSCRIPT_COUNTER_2": 6026, 
    "TRANSCRIPT_COUNTER_3": 2630, 
    "YES_VEP": 22573, 
    "reference_found_only": 19048, 
    "reference_found": 23041, 
    "reference_not_found": 9226, 
    "vep_concordant": 21278, 
    "TRANSCRIPT_COUNTER_8": 90, 
    "TRANSCRIPT_COUNTER_9": 31, 
    "not_reference_found_only": 9226, 
    "NO_VEP": 19541, 
    "NT__ TRANSCRIPTS WITHOUT HGVS": 42, 
    "NO_VEP_NO_TR": 8777, 
    "YES_VEP_YES_TR": 21503, 
    "NT__ TRANSCRIPTS MORE THAN ONE": 320, 
    "TRANSCRIPT_COUNTER_1": 21896, 
    "vep_discordant": 3652, 
    "hgvs_reference_SAME_VEP": 22572, 
    "NT__ TRANSCRIPTS WITH HGVS": 880, 
    "reference_found_and_reference_not_found": 3993, 
    "transvar_found_something": 32267, 
    "more_than_one": 10371, 
    "not_vep_concordant_and_discordant": 225, 
    "COULD NOT FIND HGVS": 2384, 
    "vep_concordant_and_not_discordant": 17851, 
    "TRANSCRIPT_COUNTER_13": 6, 
    "NT__ TRANSCRIPTS ALL PERFECT AND VERSION": 318, 
    "ALL_PERFECT": 17850, 
    "NT__ TRANSCRIPTS WITH HGVS AND VERSION": 652, 
    "MUTALYZER FAILED": 307, 
    "NT__ TRANSCRIPTS ALL PERFECT": 410, 
    "YES_TR": 32267, 
    "TRANSCRIPT_COUNTER_19": 3, 
    "MUTALYZER MISMATCHED POSITION": 22, 
    "TRANSCRIPT_COUNTER_15": 4, 
    "TRANSCRIPT_COUNTER_16": 7, 
    "NO_TR": 9847, 
    "TRANSCRIPT_COUNTER_10": 22, 
    "TRANSCRIPT_COUNTER_11": 26, 
    "TRANSCRIPT_COUNTER_12": 15, 
    "YES_VEP_NO_TR": 1070, 
    "MUTALYZER_OK": 177, 
    "NO_VEP_YES_TR": 10764, 
    "TRANSCRIPT_COUNTER_14": 4, 
    "hgvs_reference_NOT_PRESENT_IN_VEP": 1, 
    "vep_concordant_and_discordant": 3427
}
Length of vep_tr_transcripts: 21503



In [52]:

    
def vep_parse_post(hgvs):

 
    server = "https://grch37.rest.ensembl.org"
    ext = "/vep/human/hgvs"
    headers={ "Content-Type" : "application/json", "Accept" : "application/json"}
    
    assert type(hgvs) is list
    #data = '[' + ','.join([rept(x) for x in hgvs]) + ']'
    data = json.dumps({"hgvs_notations": hgvs})
    print data
    
    r = requests.post(server+ext, headers=headers, data=data)
 
    if not r.ok:
        print ('ERROR:')
        print (r.text)
        return None
 
    decoded = r.json()
    return decoded



In [54]:

    
vep_parse_post(['TGFBR2:c.1381T>C'])









    



{"hgvs_notations": ["TGFBR2:c.1381T>C"]}






    Out[54]:





[{u'allele_string': u'T/C',
  u'assembly_name': u'GRCh37',
  u'end': 30715648,
  u'id': u'TGFBR2:c.1381T>C',
  u'input': u'TGFBR2:c.1381T>C',
  u'most_severe_consequence': u'synonymous_variant',
  u'seq_region_name': u'3',
  u'start': 30715648,
  u'strand': 1,
  u'transcript_consequences': [{u'amino_acids': u'L',
    u'biotype': u'protein_coding',
    u'cdna_end': 1688,
    u'cdna_start': 1688,
    u'cds_end': 1306,
    u'cds_start': 1306,
    u'codons': u'Ttg/Ctg',
    u'consequence_terms': [u'synonymous_variant'],
    u'gene_id': u'ENSG00000163513',
    u'gene_symbol': u'TGFBR2',
    u'gene_symbol_source': u'HGNC',
    u'hgnc_id': 11773,
    u'impact': u'LOW',
    u'protein_end': 436,
    u'protein_start': 436,
    u'strand': 1,
    u'transcript_id': u'ENST00000295754',
    u'variant_allele': u'C'},
   {u'amino_acids': u'L',
    u'biotype': u'protein_coding',
    u'cdna_end': 1664,
    u'cdna_start': 1664,
    u'cds_end': 1381,
    u'cds_start': 1381,
    u'codons': u'Ttg/Ctg',
    u'consequence_terms': [u'synonymous_variant'],
    u'gene_id': u'ENSG00000163513',
    u'gene_symbol': u'TGFBR2',
    u'gene_symbol_source': u'HGNC',
    u'hgnc_id': 11773,
    u'impact': u'LOW',
    u'protein_end': 461,
    u'protein_start': 461,
    u'strand': 1,
    u'transcript_id': u'ENST00000359013',
    u'variant_allele': u'C'}]}]



In [ ]:



In [29]:

    
!pip install matplotlib









    



Requirement already satisfied: matplotlib in /home/user/mutationinfo/localpython/lib/python2.7/site-packages
Requirement already satisfied: python-dateutil>=2.1 in /home/user/mutationinfo/localpython/lib/python2.7/site-packages (from matplotlib)
Requirement already satisfied: subprocess32 in /home/user/mutationinfo/localpython/lib/python2.7/site-packages (from matplotlib)
Requirement already satisfied: cycler>=0.10 in /home/user/mutationinfo/localpython/lib/python2.7/site-packages (from matplotlib)
Requirement already satisfied: six>=1.10 in /home/user/mutationinfo/localpython/lib/python2.7/site-packages/six-1.11.0-py2.7.egg (from matplotlib)
Requirement already satisfied: backports.functools-lru-cache in /home/user/mutationinfo/localpython/lib/python2.7/site-packages (from matplotlib)
Requirement already satisfied: pytz in /home/user/mutationinfo/localpython/lib/python2.7/site-packages (from matplotlib)
Requirement already satisfied: pyparsing!=2.0.4,!=2.1.2,!=2.1.6,>=2.0.1 in /home/user/mutationinfo/localpython/lib/python2.7/site-packages (from matplotlib)
Requirement already satisfied: numpy>=1.7.1 in /home/user/mutationinfo/localpython/lib/python2.7/site-packages (from matplotlib)
Requirement already satisfied: kiwisolver>=1.0.1 in /home/user/mutationinfo/localpython/lib/python2.7/site-packages (from matplotlib)
Requirement already satisfied: setuptools in /home/user/mutationinfo/localpython/lib/python2.7/site-packages (from kiwisolver>=1.0.1->matplotlib)



In [1]:

    
import matplotlib.pyplot as plt



In [18]:

    
!pip install py27-backports-functools_lru_cache









    



Collecting py27-backports-functools_lru_cache
  Could not find a version that satisfies the requirement py27-backports-functools_lru_cache (from versions: )
No matching distribution found for py27-backports-functools_lru_cache
You are using pip version 9.0.1, however version 9.0.2 is available.
You should consider upgrading via the 'pip install --upgrade pip' command.



In [20]:

    
import random
plt.plot([x[0] + (random.random()-0.5) for x in plot_data if x[1]>1], [x[1] + (random.random()-0.5) for x in plot_data if x[1]>1], '.', alpha=0.1)
plt.show()



In [22]:

    
!head parsed_abstracts.json









    



{"record": 1, "abstract": "The aim of this study was to characterise a novel mutation in the gene encoding RhAG in order to elucidate a molecular mechanism for Rh antigen expression and spherocytosis.Rhesus-associated glycoprotein (RhAG) is critical for maintaining the structure and stability of erythrocytes. Single missense mutations in the gene encoding RhAG are sufficient to induce spherocytosis and deficiencies in Rh complex formation. We report a novel missense mutation that incompletely disrupts Rh antigen expression and selectively knocks out RhD antigen expression.Blood samples were taken from a 38-year-old male, his brother, his wife and his daughter in Xi'an, China. To detect the proband's RhAG and D antigen expression, the RBC were stained with anti-D and anti-RhAG and analysed by flow cytometry. Red blood cell morphology was detected with atomic force microscopy (AFM). Genomic DNA was isolated from whole blood samples, and the RHD, RHCE and RHAG alleles were sequenced and analysed. The mutation was mapped onto a predicted crystal structure of RhAG by the I-TASSER server and visualised using PyMOL.Morphological testing by AFM found clear evidence of spherocytosis in the proband's erythrocytes. RHAG gene sequencing identified the mutation at sequence 236G\u2009>\u2009A, resulting in a serine to asparagine substitution at residue 79 (S79N). Family survey indicated that inheriting this allele is necessary and sufficient to cause the condition. Mapping the mutation onto a predicted crystal structure of RhAG revealed the proximity of the mutation to the critical structural elements of the protein.A novel RHAG mutation significantly lowers RhAG antigen expression and antigen-mediated agglutination intensity.", "gene": "RHAG", "transcripts": [], "hgvs": "236G>A"}
{"record": 2, "abstract": "We aimed to identify mutations associated with osteochondromatosis in a litter of American Staffordshire Terrier puppies.We hypothesized that the associated mutation would be located in a gene that causes osteochondromatosis in humans.A litter of 9 American Staffordshire puppies, their sire and dam, 3 of 4 grandparents, 26 healthy unrelated American Staffordshire Terriers, and 154 dogs of 27 different breeds.Whole genome sequencing was performed on the proband, and variants were compared against polymorphisms derived from 154 additional dogs across 27 breeds, as well as single nucleotide polymorphism database 146. One variant was selected for follow-up sequencing. Parentage and genetic mosaicism were evaluated across the litter.We found 56,301 genetic variants unique to the proband. Eleven variants were located in or near the gene exostosin 2 (EXT2), which is strongly associated with osteochondromatosis in humans. One heterozygous variant (c.969C\u2009>\u2009A) is predicted to result in a stop codon in exon 5 of the gene. Sanger sequencing identified the identical mutation in all affected offspring. The mutation was absent in the unaffected offspring, both parents, all available grandparents, and 26 healthy unrelated American Staffordshire Terriers.These findings represent the first reported mutation associated with osteochondromatosis in dogs. Because this mutation arose de novo, the identical mutation is unlikely to be the cause of osteochondromatosis in other dogs. However, de novo mutations in EXT2 are common in humans with osteochondromatosis, and by extension, it is possible that dogs with osteochondromatosis could be identified by sequencing the entire EXT2 gene.", "gene": "EXT2", "transcripts": [], "hgvs": "c.969C>A"}
{"record": 3, "abstract": "Dystrophic epidermolysis bullosa (DEB), pretibial, a rare subtype of epidermolysis bullosa (EB), is characterized by recurrent blisters and erosions predominantly on the pretibial region. We report the case of a 60-year-old Japanese woman with persistent blistering eruptions and scar formation on the pretibial region and elbows. Mutational analysis revealed a previously reported c.5797C>T mutation in exon 70 (p.R1933X) and a novel c.6348+1G>A mutation in intron 76 of COL7A1. Reverse transcription polymerase chain reaction revealed that the c.6348+1G>A mutation resulted in the skipping of exon 76 (69 bp) and the retention of intron 76 (75 bp), and both transcripts were in-frame. From these results, we diagnosed the patient as having recessive DEB, pretibial. A review of previously reported mutations in DEB, pretibial, revealed that one-third of DEB, pretibial, cases showed a recessive inheritance pattern, and no case had a combination of premature termination codon (PTC)/PTC mutations. The DEB, pretibial, case described herein is the first reported case of a compound heterozygote with PTC/in-frame mutations. Although no special characteristic features of the mutations were identified, a high diversity of COL7A1 mutations was shown even in DEB, pretibial.", "gene": "COL7A1", "transcripts": [], "hgvs": "c.5797C>T"}
{"record": 4, "abstract": "Dystrophic epidermolysis bullosa (DEB), pretibial, a rare subtype of epidermolysis bullosa (EB), is characterized by recurrent blisters and erosions predominantly on the pretibial region. We report the case of a 60-year-old Japanese woman with persistent blistering eruptions and scar formation on the pretibial region and elbows. Mutational analysis revealed a previously reported c.5797C>T mutation in exon 70 (p.R1933X) and a novel c.6348+1G>A mutation in intron 76 of COL7A1. Reverse transcription polymerase chain reaction revealed that the c.6348+1G>A mutation resulted in the skipping of exon 76 (69 bp) and the retention of intron 76 (75 bp), and both transcripts were in-frame. From these results, we diagnosed the patient as having recessive DEB, pretibial. A review of previously reported mutations in DEB, pretibial, revealed that one-third of DEB, pretibial, cases showed a recessive inheritance pattern, and no case had a combination of premature termination codon (PTC)/PTC mutations. The DEB, pretibial, case described herein is the first reported case of a compound heterozygote with PTC/in-frame mutations. Although no special characteristic features of the mutations were identified, a high diversity of COL7A1 mutations was shown even in DEB, pretibial.", "gene": "COL7A1", "transcripts": [], "hgvs": "c.6348+1G>A"}
{"record": 5, "abstract": "Dystrophic epidermolysis bullosa (DEB), pretibial, a rare subtype of epidermolysis bullosa (EB), is characterized by recurrent blisters and erosions predominantly on the pretibial region. We report the case of a 60-year-old Japanese woman with persistent blistering eruptions and scar formation on the pretibial region and elbows. Mutational analysis revealed a previously reported c.5797C>T mutation in exon 70 (p.R1933X) and a novel c.6348+1G>A mutation in intron 76 of COL7A1. Reverse transcription polymerase chain reaction revealed that the c.6348+1G>A mutation resulted in the skipping of exon 76 (69 bp) and the retention of intron 76 (75 bp), and both transcripts were in-frame. From these results, we diagnosed the patient as having recessive DEB, pretibial. A review of previously reported mutations in DEB, pretibial, revealed that one-third of DEB, pretibial, cases showed a recessive inheritance pattern, and no case had a combination of premature termination codon (PTC)/PTC mutations. The DEB, pretibial, case described herein is the first reported case of a compound heterozygote with PTC/in-frame mutations. Although no special characteristic features of the mutations were identified, a high diversity of COL7A1 mutations was shown even in DEB, pretibial.", "gene": "COL7A1", "transcripts": [], "hgvs": "c.6348+1G>A"}
{"record": 6, "abstract": "To identify the pathogenic mutation underlying microcephaly primary hereditary (MCPH) in a large consanguineous Pakistani family.A five-generation family with an autosomal recessive transmission of MCPH was recruited. Targeted next-generation DNA sequencing was carried out to analyze the genomic DNA sample from the proband with MCPH using a previously designed panel targeting 46 known microcephaly-causing genes. Sanger sequencing was performed to verify all identified variants.We found a novel homozygous nonsense mutation, c.7543C>T, in the ASPM gene. This mutation led to the substitution of an arginine with a stop codon at amino acid residue 2515 (p.Arg2515Ter). The mutation cosegregated with the MCPH phenotype in all affected and obligate carrier family members, but was not present in public databases (dbSNP147, Exome Variant Server, the 1000 Genomes Project, Exome Aggregation Consortium, Human Gene Mutation Database, and ClinVar) or 200 control individuals. The c.7543C>T mutation in ASPM may activate nonsense-mediated mRNA decay pathways and could underlie the pathogenesis of MCPH through a loss-of-function mechanism.The c.7543C>T (p.Arg2515Ter) mutation in ASPM is a novel pathogenic mutation for the typical MCPH phenotype in this family.", "gene": "ASPM", "transcripts": [], "hgvs": "c.7543C>T"}
{"record": 7, "abstract": "To identify the pathogenic mutation underlying microcephaly primary hereditary (MCPH) in a large consanguineous Pakistani family.A five-generation family with an autosomal recessive transmission of MCPH was recruited. Targeted next-generation DNA sequencing was carried out to analyze the genomic DNA sample from the proband with MCPH using a previously designed panel targeting 46 known microcephaly-causing genes. Sanger sequencing was performed to verify all identified variants.We found a novel homozygous nonsense mutation, c.7543C>T, in the ASPM gene. This mutation led to the substitution of an arginine with a stop codon at amino acid residue 2515 (p.Arg2515Ter). The mutation cosegregated with the MCPH phenotype in all affected and obligate carrier family members, but was not present in public databases (dbSNP147, Exome Variant Server, the 1000 Genomes Project, Exome Aggregation Consortium, Human Gene Mutation Database, and ClinVar) or 200 control individuals. The c.7543C>T mutation in ASPM may activate nonsense-mediated mRNA decay pathways and could underlie the pathogenesis of MCPH through a loss-of-function mechanism.The c.7543C>T (p.Arg2515Ter) mutation in ASPM is a novel pathogenic mutation for the typical MCPH phenotype in this family.", "gene": "ASPM", "transcripts": [], "hgvs": "c.7543C>T"}
{"record": 8, "abstract": "To identify the pathogenic mutation underlying microcephaly primary hereditary (MCPH) in a large consanguineous Pakistani family.A five-generation family with an autosomal recessive transmission of MCPH was recruited. Targeted next-generation DNA sequencing was carried out to analyze the genomic DNA sample from the proband with MCPH using a previously designed panel targeting 46 known microcephaly-causing genes. Sanger sequencing was performed to verify all identified variants.We found a novel homozygous nonsense mutation, c.7543C>T, in the ASPM gene. This mutation led to the substitution of an arginine with a stop codon at amino acid residue 2515 (p.Arg2515Ter). The mutation cosegregated with the MCPH phenotype in all affected and obligate carrier family members, but was not present in public databases (dbSNP147, Exome Variant Server, the 1000 Genomes Project, Exome Aggregation Consortium, Human Gene Mutation Database, and ClinVar) or 200 control individuals. The c.7543C>T mutation in ASPM may activate nonsense-mediated mRNA decay pathways and could underlie the pathogenesis of MCPH through a loss-of-function mechanism.The c.7543C>T (p.Arg2515Ter) mutation in ASPM is a novel pathogenic mutation for the typical MCPH phenotype in this family.", "gene": "ASPM", "transcripts": [], "hgvs": "c.7543C>T"}
{"record": 9, "abstract": "Autosomal recessive woolly hair is a relatively rare hereditary hair disorder characterized by sparse, short, curly hair. This condition is known to be caused by mutations in the LIPH gene, LPAR6 gene or KRT25 gene. In the Japanese population, most patients with autosomal recessive woolly hair carry one of two founder mutations in the LIPH gene, c.736T>A (p.Cys246Ser) or c.742C>A (p.His248Asn). However, occasionally, individuals with this condition carry compound heterozygous mutations, typically one founder mutation and another mutation. In this study, we describe a patient with a compound heterozygous mutation in the LIPH gene at c.736T>A and c.1095-3C>G. The latter mutation created a novel splice site. This was the fourth splice site mutation to be described in the LIPH gene. Furthermore, we performed an in vitro transcription assay in cultured cells, and demonstrated that the c.1095-3C>G mutation led to a frame-shift, which created a premature termination codon at the protein level (p.Glu366Ilefs*7). Finally, we summarized the mutations previously reported for the LIPH gene. Our findings provide further clues as to the molecular basis of autosomal recessive woolly hair.", "gene": "LIPH", "transcripts": [], "hgvs": "c.736T>A"}
{"record": 10, "abstract": "Autosomal recessive woolly hair is a relatively rare hereditary hair disorder characterized by sparse, short, curly hair. This condition is known to be caused by mutations in the LIPH gene, LPAR6 gene or KRT25 gene. In the Japanese population, most patients with autosomal recessive woolly hair carry one of two founder mutations in the LIPH gene, c.736T>A (p.Cys246Ser) or c.742C>A (p.His248Asn). However, occasionally, individuals with this condition carry compound heterozygous mutations, typically one founder mutation and another mutation. In this study, we describe a patient with a compound heterozygous mutation in the LIPH gene at c.736T>A and c.1095-3C>G. The latter mutation created a novel splice site. This was the fourth splice site mutation to be described in the LIPH gene. Furthermore, we performed an in vitro transcription assay in cultured cells, and demonstrated that the c.1095-3C>G mutation led to a frame-shift, which created a premature termination codon at the protein level (p.Glu366Ilefs*7). Finally, we summarized the mutations previously reported for the LIPH gene. Our findings provide further clues as to the molecular basis of autosomal recessive woolly hair.", "gene": "LIPH", "transcripts": [], "hgvs": "c.742C>A"}