NM_004004.6(GJB2):c.200dup (p.His67fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 4, 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:: RCV001390692.7

Allele description [Variation Report for NM_004004.6(GJB2):c.200dup (p.His67fs)]

NM_004004.6(GJB2):c.200dup (p.His67fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.200dup (p.His67fs)

HGVS:

NC_000013.11:g.20189382dup
NG_008358.1:g.8594dup
NM_004004.6:c.200dupMANE SELECT
NP_003995.2:p.His67fs
LRG_1350t1:c.200dup
LRG_1350:g.8594dup
LRG_1350p1:p.His67fs
NC_000013.10:g.20763520_20763521insT
NC_000013.10:g.20763521dup

Protein change:

H67fs

Links:

dbSNP: rs2137308372

NCBI 1000 Genomes Browser:

rs2137308372

Molecular consequence:

NM_004004.6:c.200dup - 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
SCV001592493	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 4, 2020)	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

SCV001592493

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 4, 2020)

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, SCV001592493.4

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the GJB2 protein. Other variant(s) that disrupt this region (p.Cys211Leufs*5) have been determined to be pathogenic (PMID: 9529365, 12910486, 20863150). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with GJB2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the GJB2 gene (p.His67Glnfs*35). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 160 amino acids 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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