NM_004004.6(GJB2):c.9G>A (p.Trp3Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 25, 2024
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:: RCV001852793.5

Allele description [Variation Report for NM_004004.6(GJB2):c.9G>A (p.Trp3Ter)]

NM_004004.6(GJB2):c.9G>A (p.Trp3Ter)

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.9G>A (p.Trp3Ter)

HGVS:

NC_000013.11:g.20189573C>T
NG_008358.1:g.8403G>A
NM_004004.6:c.9G>AMANE SELECT
NP_003995.2:p.Trp3Ter
LRG_1350t1:c.9G>A
LRG_1350:g.8403G>A
LRG_1350p1:p.Trp3Ter
NC_000013.10:g.20763712C>T
NM_004004.5:c.9G>A
c.9G>A
p.Trp3X

Protein change:

W3*

Links:

dbSNP: rs111033401

NCBI 1000 Genomes Browser:

rs111033401

Molecular consequence:

NM_004004.6:c.9G>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002240126	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 25, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 21488715, 28383030, 9529365, 12910486, 20863150, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002240126

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 25, 2024)

germline

clinical testing

PubMed (6)
[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

Phenotype-genotype correlation in 295 Chinese deaf subjects with biallelic causative mutations in the GJB2 gene.

Zhao FF, Ji YB, Wang DY, Lan L, Han MK, Li Q, Zhao Y, Rao S, Han D, Wang QJ.

Genet Test Mol Biomarkers. 2011 Sep;15(9):619-25. doi: 10.1089/gtmb.2010.0192. Epub 2011 Apr 13.

PubMed [citation]

PMID:: 21488715

Genetic Predisposition to Sporadic Congenital Hearing Loss in a Pediatric Population.

Jung J, Lee JS, Cho KJ, Yu S, Yoon JH, Yung Gee H, Choi JY.

Sci Rep. 2017 Apr 6;7:45973. doi: 10.1038/srep45973.

PubMed [citation]

PMID:: 28383030
PMCID:: PMC5382691

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV002240126.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Trp3*) in the GJB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 224 amino acid(s) of the GJB2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with non-syndromic deafness (PMID: 21488715, 28383030). ClinVar contains an entry for this variant (Variation ID: 44767). This variant disrupts a region of the GJB2 protein in which other variant(s) (p.Cys211Leufs*5) have been determined to be pathogenic (PMID: 9529365, 12910486, 20863150). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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 8, 2024

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