NM_004004.6(GJB2):c.493C>T (p.Arg165Trp) AND Autosomal recessive nonsyndromic hearing loss 1A

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: May 18, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV000668216.9

Allele description [Variation Report for NM_004004.6(GJB2):c.493C>T (p.Arg165Trp)]

NM_004004.6(GJB2):c.493C>T (p.Arg165Trp)

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.493C>T (p.Arg165Trp)

HGVS:

NC_000013.11:g.20189089G>A
NG_008358.1:g.8887C>T
NM_004004.6:c.493C>TMANE SELECT
NP_003995.2:p.Arg165Trp
LRG_1350t1:c.493C>T
LRG_1350:g.8887C>T
LRG_1350p1:p.Arg165Trp
NC_000013.10:g.20763228G>A
NM_004004.5:c.493C>T
P29033:p.Arg165Trp

Protein change:

R165W

Links:

UniProtKB: P29033#VAR_015942; dbSNP: rs376898963

NCBI 1000 Genomes Browser:

rs376898963

Molecular consequence:

NM_004004.6:c.493C>T - 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
SCV000382995	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Apr 27, 2017)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 15617550, 20863150, 25388846, 12746422, 11494963, 20234132, 18607988, 20086306 Citation Link,
SCV000792784	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jul 14, 2017)	unknown	clinical testing	PubMed (10) [See all records that cite these PMIDs] 20086306, 12746422, 15617550, 18607988, 20234132, 17666888, 18941476, 16950989, 20863150, 11494963 Citation Link,
SCV001138908	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Benign (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001736810	Pars Genome Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (May 18, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
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

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 novel 355-357delGAG mutation and frequency of connexin-26 (GJB2) mutations in Iranian patients.

Hamid M, Karimipoor M, Chaleshtori MH, Akbari MT.

J Genet. 2009 Dec;88(3):359-62. No abstract available.

PubMed [citation]

PMID:: 20086306

See all PubMed Citations (12)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000382995.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

#	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 Counsyl, SCV000792784.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

#	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 Mendelics, SCV001138908.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Pars Genome Lab, SCV001736810.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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