Variant Detail

Variant Information
ID
DPV: 472
Chromosome
13
Gene
HGVS (GRCh37/hg19)
NC_000013.10:g.20763612C>T
HGVS (GRCh38/hg38)
NC_000013.11:g.20189473C>T
HGVS (RNA)
NM_004004:c.109G>A
HGVS (Protein)
NP_003995:p.V37I
dbSNP
-
ClinGen Allele Registry
CA172210
Allele Frequency
Individual Information

ID
DPVS:359.1
Clinical Significance
Pathogenic
Date Last Evaluated
2015-07-06
Clinical Significance Citation
Pang, X. Characterization of spectrum, de novo rate and genotype-phenotype correlation of dominant GJB2 mutations in Chinese hans. 2014 PLoS One. 2014 Jun 19;9(6):e100483. doi: 10.1371/journal.pone.0100483. eCollection 2014. PMID:24945352
Tabor, H. K. Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results. 2014 Am J Hum Genet. 2014 Aug 7;95(2):183-93. doi: 10.1016/j.ajhg.2014.07.006. Epub 2014 Jul 31. PMID:25087612
Kelley, P. M. Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss. 1998 Am J Hum Genet. 1998 Apr;62(4):792-9. doi: 10.1086/301807. PMID:9529365
Mori, K. Social Health Insurance-Based Simultaneous Screening for 154 Mutations in 19 Deafness Genes Efficiently Identified Causative Mutations in Japanese Hearing Loss Patients. 2016 PLoS One. 2016 Sep 14;11(9):e0162230. doi: 10.1371/journal.pone.0162230. eCollection 2016. PMID:27627659

Transcript
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Disease

Phenotype
-
Zygosity
single heterozygote
Allele Origin
germline
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • SEQuencing
Collection Method
clinical testing
Compound heterozygous variant(s)
Data Submitter
Comment
-

ID
DPVS:1545.1
Clinical Significance
Pathogenic
Date Last Evaluated
2018-01-30
Clinical Significance Citation
Sakuma, N. An effective screening strategy for deafness in combination with a next-generation sequencing platform: a consecutive analysis. 2016 J Hum Genet. 2016 Mar;61(3):253-61. doi: 10.1038/jhg.2015.143. Epub 2016 Jan 14. PMID:26763877
Snoeckx, R. L. GJB2 mutations and degree of hearing loss: a multicenter study. 2005 Am J Hum Genet. 2005 Dec;77(6):945-57. doi: 10.1086/497996. Epub 2005 Oct 19. PMID:16380907
Huculak, C. V37I connexin 26 allele in patients with sensorineural hearing loss: evidence of its pathogenicity. 2006 Am J Med Genet A. 2006 Nov 15;140(22):2394-400. doi: 10.1002/ajmg.a.31486. PMID:17036313
Pollak, A. M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance. 2007 Am J Med Genet A. 2007 Nov 1;143A(21):2534-43. doi: 10.1002/ajmg.a.31982. PMID:17935238

Transcript
-
Disease

Phenotype
-
Zygosity
compound heterozygote
Allele Origin
germline
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • Next-Generation Sequencing
Collection Method
literature only
Compound heterozygous variant(s)
Data Submitter
Comment
-

ClinVar
Model Animals
VCF
VCF (GRCh37/hg19) 
											##fileformat=VCFv4.0
##reference=GRCh37
##INFO=<ID=CLNALLELEID,Number=1,Type=Integer,Description="the ClinVar Allele ID">
##INFO=<ID=CLNDISDB,Number=.,Type=String,Description="Tag-value pairs of disease database name and identifier, e.g. OMIM:NNNNNN (from ClinVar)">
##INFO=<ID=CLNDN,Number=.,Type=String,Description="ClinVar's preferred disease name for the concept specified by disease identifiers in CLNDISDB (from ClinVar)">
##INFO=<ID=CLNHGVS,Number=.,Type=String,Description="Top-level (primary assembly, alt, or patch) HGVS expression.(from ClinVar)">
##INFO=<ID=CLNSIG,Number=.,Type=String,Description="Clinical significance for this single variant (from ClinVar)">
##INFO=<ID=EXAC_AC,Number=A,Type=Integer,Description="Allele count in genotypes, for each ALT allele, in the same order as listed (from ExAC r1)">
##INFO=<ID=EXAC_AF,Number=A,Type=Float,Description="Allele Frequency, for each ALT allele, in the same order as listed (from ExAC r1)">
##INFO=<ID=EXAC_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from ExAC r1)">
##INFO=<ID=EXAC_FILTER,Number=1,Type=String,Description="calculated by self of overlapping values in field FILTER (from ExAC r1)">
##INFO=<ID=GNOMAD_AC,Number=A,Type=Integer,Description="Allele count in genotypes, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AF,Number=A,Type=Float,Description="Allele Frequency, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from gnomAD v2.1.1 )">
##INFO=<ID=HGVD_AAF,Number=A,Type=Float,Description="Alternative Allele Frequency(s) NA/(NR+NAtotal) (from HGVD/DBexome20170802)">
##INFO=<ID=HGVD_AC,Number=A,Type=Integer,Description="number(s) of alternative allele(s) (from HGVD/DBexome20170802)">
##INFO=<ID=HGVD_NR,Number=1,Type=Integer,Description="number of reference allele (from HGVD/DBexome20170802)">
##INFO=<ID=TOMMO_4_7K_AC,Number=A,Type=Integer,Description="Allele count in genotypes (from ToMMo 4.7KJPN (20190826))">
##INFO=<ID=TOMMO_4_7K_AF,Number=A,Type=Float,Description="Allele frequency, for each ALT allele, in the same order as listed  (from ToMMo 4.7KJPN (20190826))">
##INFO=<ID=TOMMO_4_7K_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from ToMMo 4.7KJPN (20190826))">
##INFO=<ID=dbSNP_RSID,Number=1,Type=String,Description="dbSNP ID (from dbSNP b151 )">
##INFO=<ID=GENEINFO,Number=1,Type=String,Description="Pairs each of gene symbol:gene id. The gene symbol and id are delimited by a colon (:)">
##INFO=<ID=DPVID,Number=.,Type=String,Description="DPV Variant ID">
##INFO=<ID=DPVSIG,Number=.,Type=String,Description="Variant Clinical Significance">
##INFO=<ID=DPVDSDBID,Number=.,Type=String,Description="Variant disease database ID">
##INFO=<ID=DPVDBN,Number=.,Type=String,Description="Variant disease name">
##INFO=<ID=DPVHGVS,Number=.,Type=String,Description="Variant in HGVS.">
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
13	20763612	NC_000013.10:g.20763612C>T	C	T	.	.	EXAC_AF=0.006581;EXAC_AC=799;EXAC_AN=121412;GNOMAD_AF=0.0077203;GNOMAD_AC=1936;GNOMAD_AN=250766;TOMMO_4_7K_AF=0.0112;TOMMO_4_7K_AC=107;TOMMO_4_7K_AN=9546;CLNALLELEID=32062;CLNDN=Hearing_impairment|Mutilating_keratoderma|Keratitis-ichthyosis-deafness_syndrome,_autosomal_dominant|Palmoplantar_keratoderma-deafness_syndrome|Knuckle_pads,_deafness_AND_leukonychia_syndrome|Deafness,_autosomal_recessive_1A|Deafness,_X-linked_2|Deafness,_autosomal_dominant_3a|Hystrix-like_ichthyosis_with_deafness|Deafness,_autosomal_recessive_1b|Nonsyndromic_hearing_loss_and_deafness|Nonsyndromic_Deafness|none_provided|not_provided|Rare_genetic_deafness;CLNDISDB=Human_Phenotype_Ontology:HP:0000365,Human_Phenotype_Ontology:HP:0000404,Human_Phenotype_Ontology:HP:0001728,Human_Phenotype_Ontology:HP:0001729,Human_Phenotype_Ontology:HP:0001754,Human_Phenotype_Ontology:HP:0008560,Human_Phenotype_Ontology:HP:0008563,MONDO:MONDO:0005365,MedGen:C1384666|MONDO:MONDO:0007422,MedGen:C0265964,OMIM:124500,Orphanet:ORPHA494,SNOMED_CT:24559001|MONDO:MONDO:0007850,MedGen:C0265336,OMIM:148210|MONDO:MONDO:0007852,MedGen:C1835672,OMIM:148350,Orphanet:ORPHA2202|MONDO:MONDO:0007866,MedGen:C0266004,OMIM:149200,Orphanet:ORPHA2698,SNOMED_CT:1271009|MONDO:MONDO:0009076,MedGen:C2673759,OMIM:220290|MONDO:MONDO:0010576,MedGen:C1844678,OMIM:304400,Orphanet:ORPHA383|MONDO:MONDO:0011103,MedGen:C2675750,OMIM:601544|MONDO:MONDO:0011245,MedGen:C1865234,OMIM:602540|MONDO:MONDO:0012977,MedGen:C2675235,OMIM:612645|MONDO:MONDO:0019497,MedGen:CN043648,Orphanet:ORPHA87884|MeSH:C580334,MedGen:C3711374|MedGen:CN235283|MedGen:CN517202|MedGen:CN826980,Orphanet:ORPHA96210;CLNSIG=Pathogenic;CLNHGVS=NC_000013.10:g.20763612C>T;HGVD_AAF=0.006198;HGVD_NR=2405;HGVD_AC=15;GENEINFO=4284:2706;DPVID=472;DPVSIG=Pathogenic;DPVDSDBID=MedGen:C0018772|OMIM:220290;DPVDBN=Partial_deafness|Deafness\x2c_autosomal_recessive\x2c_1A;DPVHGVS=NC_000013.10:g.20763612C>T	.
VCF (GRCh38/hg38) 
											##fileformat=VCFv4.0
##reference=GRCh38
##INFO=<ID=CLNALLELEID,Number=1,Type=Integer,Description="the ClinVar Allele ID">
##INFO=<ID=CLNDISDB,Number=.,Type=String,Description="Tag-value pairs of disease database name and identifier, e.g. OMIM:NNNNNN (from ClinVar)">
##INFO=<ID=CLNDN,Number=.,Type=String,Description="ClinVar's preferred disease name for the concept specified by disease identifiers in CLNDISDB (from ClinVar)">
##INFO=<ID=CLNHGVS,Number=.,Type=String,Description="Top-level (primary assembly, alt, or patch) HGVS expression.(from ClinVar)">
##INFO=<ID=CLNSIG,Number=.,Type=String,Description="Clinical significance for this single variant (from ClinVar)">
##INFO=<ID=GNOMAD_AC,Number=A,Type=Integer,Description="Allele count in genotypes, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AF,Number=A,Type=Float,Description="Allele Frequency, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from gnomAD v2.1.1 )">
##INFO=<ID=dbSNP_RSID,Number=1,Type=String,Description="dbSNP ID (from dbSNP b151 )">
##originalFile=</tmp/crossmap-input-ve_0pfeq>
##targetRefGenome=</usr/lib64/python2.7/site-packages/transvar/transvar.download/hg38.fa>
##INFO=<ID=GENEINFO,Number=1,Type=String,Description="Pairs each of gene symbol:gene id. The gene symbol and id are delimited by a colon (:)">
##INFO=<ID=DPVID,Number=.,Type=String,Description="DPV Variant ID">
##INFO=<ID=DPVSIG,Number=.,Type=String,Description="Variant Clinical Significance">
##INFO=<ID=DPVDSDBID,Number=.,Type=String,Description="Variant disease database ID">
##INFO=<ID=DPVDBN,Number=.,Type=String,Description="Variant disease name">
##INFO=<ID=DPVHGVS,Number=.,Type=String,Description="Variant in HGVS.">
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
13	20189473	NC_000013.10:g.20763612C>T	C	T	.	.	dbSNP_RSID=rs72474224;GNOMAD_AF=0.0077203;GNOMAD_AC=1936;GNOMAD_AN=250766;CLNALLELEID=32062;CLNDN=Hearing_impairment|Mutilating_keratoderma|Keratitis-ichthyosis-deafness_syndrome,_autosomal_dominant|Palmoplantar_keratoderma-deafness_syndrome|Knuckle_pads,_deafness_AND_leukonychia_syndrome|Deafness,_autosomal_recessive_1A|Deafness,_autosomal_dominant_3a|Hystrix-like_ichthyosis_with_deafness|Deafness,_autosomal_recessive_1b|Nonsyndromic_hearing_loss_and_deafness|Nonsyndromic_Deafness|Deafness,_X-linked_2|none_provided|not_provided|Rare_genetic_deafness;CLNDISDB=Human_Phenotype_Ontology:HP:0000365,Human_Phenotype_Ontology:HP:0000404,Human_Phenotype_Ontology:HP:0001728,Human_Phenotype_Ontology:HP:0001729,Human_Phenotype_Ontology:HP:0001754,Human_Phenotype_Ontology:HP:0008560,Human_Phenotype_Ontology:HP:0008563,MONDO:MONDO:0005365,MedGen:C1384666|MONDO:MONDO:0007422,MedGen:C0265964,OMIM:124500,Orphanet:ORPHA494,SNOMED_CT:24559001|MONDO:MONDO:0007850,MedGen:C0265336,OMIM:148210|MONDO:MONDO:0007852,MedGen:C1835672,OMIM:148350,Orphanet:ORPHA2202|MONDO:MONDO:0007866,MedGen:C0266004,OMIM:149200,Orphanet:ORPHA2698,SNOMED_CT:1271009|MONDO:MONDO:0009076,MedGen:C2673759,OMIM:220290|MONDO:MONDO:0011103,MedGen:C2675750,OMIM:601544|MONDO:MONDO:0011245,MedGen:C1865234,OMIM:602540|MONDO:MONDO:0012977,MedGen:C2675235,OMIM:612645|MONDO:MONDO:0019497,MedGen:CN043648,Orphanet:ORPHA87884|MeSH:C580334,MedGen:C3711374|MedGen:C1844678,OMIM:304400|MedGen:CN235283|MedGen:CN517202|MedGen:CN826980,Orphanet:ORPHA96210;CLNSIG=Pathogenic;CLNHGVS=NC_000013.11:g.20189473C>T;GENEINFO=4284:2706;DPVID=472;DPVSIG=Pathogenic;DPVDSDBID=MedGen:C0018772|OMIM:220290;DPVDBN=Partial_deafness|Deafness\x2c_autosomal_recessive\x2c_1A;DPVHGVS=NC_000013.11:g.20189473C>T	.