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NM_004004.6(GJB2):c.476A>T (p.Asp159Val) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 28, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002222355.1

Allele description [Variation Report for NM_004004.6(GJB2):c.476A>T (p.Asp159Val)]

NM_004004.6(GJB2):c.476A>T (p.Asp159Val)

Gene:
GJB2:gap junction protein beta 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q12.11
Genomic location:
Preferred name:
NM_004004.6(GJB2):c.476A>T (p.Asp159Val)
HGVS:
  • NC_000013.11:g.20189106T>A
  • NG_008358.1:g.8870A>T
  • NM_004004.6:c.476A>TMANE SELECT
  • NP_003995.2:p.Asp159Val
  • LRG_1350t1:c.476A>T
  • LRG_1350:g.8870A>T
  • LRG_1350p1:p.Asp159Val
  • NC_000013.10:g.20763245T>A
  • NM_004004.5:c.476A>T
  • P29033:p.Asp159Val
Protein change:
D159V; ASP159VAL
Links:
UniProtKB: P29033#VAR_015941; OMIM: 121011.0024; dbSNP: rs28931592
NCBI 1000 Genomes Browser:
rs28931592
Molecular consequence:
  • NM_004004.6:c.476A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002500697Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Mar 28, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Exploring the clinical and epidemiological complexity of GJB2-linked deafness.

Gualandi F, Ravani A, Berto A, Sensi A, Trabanelli C, Falciano F, Trevisi P, Mazzoli M, Tibiletti MG, Cristofari E, Burdo S, Ferlini A, Martini A, Calzolari E.

Am J Med Genet. 2002 Sep 15;112(1):38-45.

PubMed [citation]
PMID:
12239718

Residual Hearing in DFNB1 Deafness and Its Clinical Implication in a Korean Population.

Kim SY, Kim AR, Han KH, Kim MY, Jeon EH, Koo JW, Oh SH, Choi BY.

PLoS One. 2015;10(6):e0125416. doi: 10.1371/journal.pone.0125416.

PubMed [citation]
PMID:
26061264
PMCID:
PMC4464755
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002500697.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: GJB2 c.476A>T (p.Asp159Val) results in a non-conservative amino acid change located in the cysteine-rich domain (IPR019570) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251102 control chromosomes (gnomAD). c.476A>T has been reported in the literature in at least two compound heterozygous individuals affected with Non-Syndromic Hearing Loss (Gualandi_2002, Kim_2015, Lee_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as of uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024