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NM_004004.6(GJB2):c.139G>T (p.Glu47Ter) AND Nonsyndromic genetic hearing loss

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 21, 2020
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:
RCV001257036.9

Allele description [Variation Report for NM_004004.6(GJB2):c.139G>T (p.Glu47Ter)]

NM_004004.6(GJB2):c.139G>T (p.Glu47Ter)

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.139G>T (p.Glu47Ter)
HGVS:
  • NC_000013.11:g.20189443C>A
  • NG_008358.1:g.8533G>T
  • NM_004004.6:c.139G>TMANE SELECT
  • NP_003995.2:p.Glu47Ter
  • LRG_1350t1:c.139G>T
  • LRG_1350:g.8533G>T
  • LRG_1350p1:p.Glu47Ter
  • NC_000013.10:g.20763582C>A
  • NM_004004.5:c.139G>T
  • NP_003995.2:p.Glu47*
  • c.139G>T
  • p.(Glu47*)
  • p.Glu47X
Protein change:
E47*; GLU47TER
Links:
OMIM: 121011.0006; dbSNP: rs104894398
NCBI 1000 Genomes Browser:
rs104894398
Molecular consequence:
  • NM_004004.6:c.139G>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
6

Condition(s)

Name:
Nonsyndromic genetic hearing loss
Synonyms:
Nonsyndromic hearing loss and deafness; Non-syndromic genetic deafness; Nonsyndromic genetic deafness
Identifiers:
MONDO: MONDO:0019497; MedGen: C5680182; Orphanet: 87884

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001433541INGEBI, INGEBI / CONICET
criteria provided, single submitter

(ClinGen HL ACMG Specifications v1)		Pathogenic
(Aug 21, 2020) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
Caucasiangermlineyes6not providednot providednot providednot providedclinical testing

Citations

PubMed

Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene.

Denoyelle F, Weil D, Maw MA, Wilcox SA, Lench NJ, Allen-Powell DR, Osborn AH, Dahl HH, Middleton A, Houseman MJ, Dodé C, Marlin S, Boulila-ElGaïed A, Grati M, Ayadi H, BenArab S, Bitoun P, Lina-Granade G, Godet J, Mustapha M, Loiselet J, El-Zir E, et al.

Hum Mol Genet. 1997 Nov;6(12):2173-7.

PubMed [citation]
PMID:
9336442

Mutations of GJB2 in three geographic isolates from northern Tunisia: evidence for genetic heterogeneity within isolates.

Ben Arab S, Hmani M, Denoyelle F, Boulila-Elgaied A, Chardenoux S, Hachicha S, Petit C, Ayadi H.

Clin Genet. 2000 Jun;57(6):439-43.

PubMed [citation]
PMID:
10905664
See all PubMed Citations (6)

Details of each submission

From INGEBI, INGEBI / CONICET, SCV001433541.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Caucasian6not providednoclinical testing PubMed (6)

Description

Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filtering allele frequency of the c.139 G>T (p.Glu47*) variant in the GJB2 gene is 0.02% (13/35412) of Latino chromosomes by the Genome Aggregation Database http://gnomad.broadinstitute.org; (calculated by using inverse allele frequency at ttps://www.cardiodb.org/allelefrequencyapp/), which meets the PM2_Supporting rule. The p.Glu47* variant is predicted to cause a premature stop codon in the only exon of GJB2 that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism of disease (PVS1). This variant has been detected in patients with hearing loss in trans with at least 4 pathogenic or suspected-pathogenic variants (PM3_VeryStrong; PMID: 9336442, 10905664, 12910486, 14985372, 24158611). The c.139G>T variant meets criteria to be classified as pathogenic for autosomal recessive non-syndromic hearing loss: (PVS1, PM2_Supporting, PM3_VeryStrong).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providedbloodnot provided6not providednot providednot provided

Last Updated: Nov 3, 2024