NM_004004.6(GJB2):c.11del (p.Gly4fs) AND Autosomal recessive nonsyndromic hearing loss 1A

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 5, 2016
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:: RCV000588025.1

Allele description [Variation Report for NM_004004.6(GJB2):c.11del (p.Gly4fs)]

NM_004004.6(GJB2):c.11del (p.Gly4fs)

Gene:

GJB2:gap junction protein beta 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.11del (p.Gly4fs)

HGVS:

NC_000013.10:g.20763710del
NC_000013.11:g.20189574del
NG_008358.1:g.8405del
NM_004004.6:c.11delMANE SELECT
NP_003995.2:p.Gly4fs
LRG_1350t1:c.11del
LRG_1350:g.8405del
LRG_1350p1:p.Gly4fs
NC_000013.10:g.20763710del
NC_000013.10:g.20763713del
NC_000013.10:g.20763713delC
NM_004004.5:c.11del
NM_004004.5:c.11delG

Protein change:

G4fs

Links:

dbSNP: rs1555342014

NCBI 1000 Genomes Browser:

rs1555342014

Molecular consequence:

NM_004004.6:c.11del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000698226	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Apr 5, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000698226

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Apr 5, 2016)

germline

clinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

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

Citations

PubMed

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000698226.1

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

Description

Variant summary: This GJB2 c.11delG variant causes a frameshift, which alters the proteins amino acid sequence beginning at position 4 and leads to a premature termination codon nine amino acids downstream. Mutation taster predicts this variant to be disease-causing. The variant was not observed in the large and broad cohorts of the ExAC project or ESP. The variant of interest was reported in 2 patients with hearing loss (Putcha_GenMed_2007, Banjara_IJOHNS_2015). Truncations downstream of this position have been classified as disease/pathogenic variants by our laboratory such as c.19C>T (p.Gln7X ), c.35dupG (V13fs), and c.35delG (G12fs). Deafness variation database lists the variant as "pathogenic." Considering all evidence, this variant has been classified as Likely Pathogenic until additional information becomes available.

#	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 29, 2024

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