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NM_004004.6(GJB2):c.279G>A (p.Met93Ile) AND Autosomal recessive nonsyndromic hearing loss 1A

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 5, 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:
RCV002228124.9

Allele description

NM_004004.6(GJB2):c.279G>A (p.Met93Ile)

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.279G>A (p.Met93Ile)
HGVS:
  • NC_000013.11:g.20189303C>T
  • NG_008358.1:g.8673G>A
  • NM_004004.6:c.279G>AMANE SELECT
  • NP_003995.2:p.Met93Ile
  • LRG_1350t1:c.279G>A
  • LRG_1350:g.8673G>A
  • LRG_1350p1:p.Met93Ile
  • NC_000013.10:g.20763442C>T
  • NM_004004.5:c.279G>A
  • P29033:p.Met93Ile
  • c.279G>A
Protein change:
M93I
Links:
UniProtKB: P29033#VAR_023609; dbSNP: rs397516871
NCBI 1000 Genomes Browser:
rs397516871
Molecular consequence:
  • NM_004004.6:c.279G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal recessive nonsyndromic hearing loss 1A (DFNB1A)
Synonyms:
Deafness nonsyndromic, Connexin 26 linked; Deafness, autosomal recessive 1A; DFNB 1 Nonsyndromic Hearing Loss and Deafness; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009076; MedGen: C2673759; Orphanet: 90636; OMIM: 220290

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002511672Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Apr 5, 2022) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

GJB2 mutations and degree of hearing loss: a multicenter study.

Snoeckx RL, Huygen PL, Feldmann D, Marlin S, Denoyelle F, Waligora J, Mueller-Malesinska M, Pollak A, Ploski R, Murgia A, Orzan E, Castorina P, Ambrosetti U, Nowakowska-Szyrwinska E, Bal J, Wiszniewski W, Janecke AR, Nekahm-Heis D, Seeman P, Bendova O, Kenna MA, Frangulov A, et al.

Am J Hum Genet. 2005 Dec;77(6):945-57. Epub 2005 Oct 19.

PubMed [citation]
PMID:
16380907
PMCID:
PMC1285178

A genotype-phenotype correlation for GJB2 (connexin 26) deafness.

Cryns K, Orzan E, Murgia A, Huygen PL, Moreno F, del Castillo I, Chamberlin GP, Azaiez H, Prasad S, Cucci RA, Leonardi E, Snoeckx RL, Govaerts PJ, Van de Heyning PH, Van de Heyning CM, Smith RJ, Van Camp G.

J Med Genet. 2004 Mar;41(3):147-54.

PubMed [citation]
PMID:
14985372
PMCID:
PMC1735685
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002511672.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: GJB2 c.279G>A (p.Met93Ile) results in a conservative amino acid change located in the Connexin, N-terminal domain (IPR013092) 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 1.6e-05 in 251190 control chromosomes. c.279G>A has been reported in the literature in individuals affected with Autosomal Recessive Non-Syndromic Hearing Loss (example, Wu_2002, Cryns_2004, Snoeckx_2005, Tsukada_2010). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Jun 17, 2024