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

Germline classification:: Likely pathogenic (2 submissions)
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:: RCV000675160.10

Allele description [Variation Report for NM_004004.6(GJB2):c.279G>A (p.Met93Ile)]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000800777	Counsyl	no assertion criteria provided	Likely pathogenic (Jul 17, 2017)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20497192, 14985372, 18776652, 22592158, 12172394
SCV002511672	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Apr 5, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16380907, 14985372, 12172394, 20497192 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000800777

Counsyl

no assertion criteria provided

Likely pathogenic
(Jul 17, 2017)

unknown

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002511672

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Apr 5, 2022)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

GJB2 mutations in Baluchi population.

Naghavi A, Nishimura C, Kahrizi K, Riazalhosseini Y, Bazazzadegan N, Mohseni M, Smith RJ, Najmabadi H.

J Genet. 2008 Aug;87(2):195-7. No abstract available.

PubMed [citation]

PMID:: 18776652

Porokeratotic eccrine nevus may be caused by somatic connexin26 mutations.

Easton JA, Donnelly S, Kamps MA, Steijlen PM, Martin PE, Tadini G, Janssens R, Happle R, van Geel M, van Steensel MA.

J Invest Dermatol. 2012 Sep;132(9):2184-91. doi: 10.1038/jid.2012.143. Epub 2012 May 17.

PubMed [citation]

PMID:: 22592158
PMCID:: PMC3422696

See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000800777.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 8, 2024

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