NM_004004.6(GJB2):c.37G>A (p.Val13Met) AND Autosomal recessive nonsyndromic hearing loss 1A

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: May 10, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000779131.7

Allele description [Variation Report for NM_004004.6(GJB2):c.37G>A (p.Val13Met)]

NM_004004.6(GJB2):c.37G>A (p.Val13Met)

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.37G>A (p.Val13Met)

HGVS:

NC_000013.11:g.20189545C>T
NG_008358.1:g.8431G>A
NM_004004.6:c.37G>AMANE SELECT
NP_003995.2:p.Val13Met
LRG_1350t1:c.37G>A
LRG_1350:g.8431G>A
LRG_1350p1:p.Val13Met
NC_000013.10:g.20763684C>T
NM_004004.5:c.37G>A

Protein change:

V13M

Links:

dbSNP: rs768130937

NCBI 1000 Genomes Browser:

rs768130937

Molecular consequence:

NM_004004.6:c.37G>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
SCV000915628	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Nov 21, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25388846, 17666888 Citation Link,
SCV001524670	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 10, 2019)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002086071	Natera, Inc.	no assertion criteria provided	Uncertain significance (Nov 3, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000915628

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Uncertain significance
(Nov 21, 2018)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV001524670

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 10, 2019)

maternal

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002086071

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Nov 3, 2020)

germline

clinical testing

Help

Summary from all submissions

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

Citations

PubMed

Bioinformatic Analysis of GJB2 Gene Missense Mutations.

Yilmaz A.

Cell Biochem Biophys. 2015 Apr;71(3):1623-42. doi: 10.1007/s12013-014-0385-7.

PubMed [citation]

PMID:: 25388846

A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort.

Putcha GV, Bejjani BA, Bleoo S, Booker JK, Carey JC, Carson N, Das S, Dempsey MA, Gastier-Foster JM, Greinwald JH Jr, Hoffmann ML, Jeng LJ, Kenna MA, Khababa I, Lilley M, Mao R, Muralidharan K, Otani IM, Rehm HL, Schaefer F, Seltzer WK, Spector EB, et al.

Genet Med. 2007 Jul;9(7):413-26.

PubMed [citation]

PMID:: 17666888

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000915628.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The GJB2 c.37G>A (p.Val13Met) missense variant was reported in a single study in a cohort of 7,401 North American individuals with hearing loss where it was found in a compound heterozygous state with a second known pathogenic missense variant in one affected individual (Putcha et al. 2007). The p.Val13Met variant occurs in a highly conserved region and is predicted by multiple prediction algorithms to be deleterious (Yilmaz et al. 2015). Control data are unavailable for this variant which is reported at a frequency of 0.00121 in the Latino population of the Exome Aggregation Consortium. Based on the limited evidence, the p.Val13Met variant is classified as a variant of unknown significance but suspicious for pathogenicity for a recessive form of nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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

From Baylor Genetics, SCV001524670.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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

From Natera, Inc., SCV002086071.1

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

#	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: Dec 24, 2023

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