NM_004004.6(GJB2):c.155_158del (p.Val52fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 27, 2023
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:: RCV003557799.2

Allele description [Variation Report for NM_004004.6(GJB2):c.155_158del (p.Val52fs)]

NM_004004.6(GJB2):c.155_158del (p.Val52fs)

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.155_158del (p.Val52fs)

HGVS:

NC_000013.11:g.20189426_20189429del
NG_008358.1:g.8549_8552del
NM_004004.6:c.155_158delMANE SELECT
NP_003995.2:p.Val52fs
LRG_1350t1:c.155_158del
LRG_1350:g.8549_8552del
LRG_1350p1:p.Val52fs
NC_000013.10:g.20763563_20763566del
NC_000013.10:g.20763565_20763568del

Protein change:

V52fs

Molecular consequence:

NM_004004.6:c.155_158del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004295454	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23141775, 18167282, 19744334, 21122151, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295454

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 27, 2023)

germline

clinical testing

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

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 novel p.Leu213X mutation in GJB2 gene in a Portuguese family.

Gonçalves AC, Chora J, Matos TD, Santos R, O'Neill A, Escada P, Fialho G, Caria H.

Int J Pediatr Otorhinolaryngol. 2013 Jan;77(1):89-91. doi: 10.1016/j.ijporl.2012.10.002. Epub 2012 Nov 8.

PubMed [citation]

PMID:: 23141775

[Mutation of GJB2 gene in nonsyndromic hearing impairment patients: analysis of 1190 cases].

Yu F, Han DY, Dai P, Kang DY, Zhang X, Liu X, Zhu QW, Yuan YY, Sun Q, Xue DD, Li M, Liu J, Yuan HJ, Yang WY.

Zhonghua Yi Xue Za Zhi. 2007 Oct 30;87(40):2814-9. Chinese.

PubMed [citation]

PMID:: 18167282

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295454.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GJB2 protein in which other variant(s) (c.Leu213*) have been determined to be pathogenic (PMID: 23141775). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individual(s) with nonsyndromic deafness (PMID: 18167282, 19744334, 21122151). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val52Alafs*29) in the GJB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 175 amino acid(s) of the GJB2 protein.

#	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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