NM_004004.6(GJB2):c.523_533del (p.Pro175fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 22, 2022
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:: RCV001382464.7

Allele description [Variation Report for NM_004004.6(GJB2):c.523_533del (p.Pro175fs)]

NM_004004.6(GJB2):c.523_533del (p.Pro175fs)

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.523_533del (p.Pro175fs)

HGVS:

NC_000013.11:g.20189052_20189062del
NG_008358.1:g.8917_8927del
NM_004004.6:c.523_533delMANE SELECT
NP_003995.2:p.Pro175fs
LRG_1350t1:c.523_533del
LRG_1350:g.8917_8927del
LRG_1350p1:p.Pro175fs
NC_000013.10:g.20763188_20763198del
NC_000013.10:g.20763191_20763201del
p.Pro175GlyfsX31

Protein change:

P175fs

Links:

dbSNP: rs876657693

NCBI 1000 Genomes Browser:

rs876657693

Molecular consequence:

NM_004004.6:c.523_533del - 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
SCV001581238	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 22, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9529365, 12910486, 20863150, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001581238

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 22, 2022)

germline

clinical testing

PubMed (4)
[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

Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss.

Kelley PM, Harris DJ, Comer BC, Askew JW, Fowler T, Smith SD, Kimberling WJ.

Am J Hum Genet. 1998 Apr;62(4):792-9.

PubMed [citation]

PMID:: 9529365
PMCID:: PMC1377046

Use of a multiplex PCR/sequencing strategy to detect both connexin 30 (GJB6) 342 kb deletion and connexin 26 (GJB2) mutations in cases of childhood deafness.

Wu BL, Kenna M, Lip V, Irons M, Platt O.

Am J Med Genet A. 2003 Aug 30;121A(2):102-8.

PubMed [citation]

PMID:: 12910486

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001581238.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Pro175Glyfs*31) in the GJB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the GJB2 protein. For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 228350). This variant has not been reported in the literature in individuals affected with GJB2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%).

#	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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