NM_004004.6(GJB2):c.407dup (p.Tyr136Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 6, 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:: RCV001870431.3

Allele description [Variation Report for NM_004004.6(GJB2):c.407dup (p.Tyr136Ter)]

NM_004004.6(GJB2):c.407dup (p.Tyr136Ter)

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.407dup (p.Tyr136Ter)

HGVS:

NC_000013.11:g.20189175dup
NG_008358.1:g.8801dup
NM_004004.6:c.407dupMANE SELECT
NP_003995.2:p.Tyr136Ter
LRG_1350t1:c.407dup
LRG_1350:g.8801dup
LRG_1350p1:p.Tyr136Ter
NC_000013.10:g.20763313_20763314insT
NC_000013.10:g.20763314dup

Protein change:

Y136*

Links:

dbSNP: rs771409330

NCBI 1000 Genomes Browser:

rs771409330

Molecular consequence:

NM_004004.6:c.407dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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UNVERIFIED_ASMBLY: Pyramimonas propulsa strain AGSB0242 small subunit ribosomal ...
UNVERIFIED_ASMBLY: Pyramimonas propulsa strain AGSB0242 small subunit ribosomal RNA gene, partial sequence; internal transcribed spacer 1, 5.8S ribosomal RNA gene, and internal transcribed spacer 2, complete sequence; and large subunit ribosomal RNA gene, partial sequence
gi|2632235345|gb|OR922727.1|

Nucleotide
Rhynchostegium sp. SH-2008 ITS1 (partial), 5.8S rRNA gene and ITS2 (partial), is...
Rhynchostegium sp. SH-2008 ITS1 (partial), 5.8S rRNA gene and ITS2 (partial), isolate SH442
gi|238654651|emb|FM212670.1|

Nucleotide
Dsc3p [Saccharomyces cerevisiae S288C]
Dsc3p [Saccharomyces cerevisiae S288C]
gi|398365837|ref|NP_014866.3|

Protein
NPBWR2 neuropeptides B and W receptor 2 [Homo sapiens]
NPBWR2 neuropeptides B and W receptor 2 [Homo sapiens]
Gene ID:2832

Gene
2832[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002120363	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 6, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 30168495, 9529365, 12910486, 20863150, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002120363

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 6, 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

Spectrum of GJB2 gene variants in Indian children with non-syndromic hearing loss.

Singh PK, Sharma S, Ghosh M, Shastri SS, Gupta N, Kabra M.

Indian J Med Res. 2018 Jun;147(6):615-618. doi: 10.4103/ijmr.IJMR_76_16. No abstract available.

PubMed [citation]

PMID:: 30168495
PMCID:: PMC6118150

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

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002120363.3

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

Description

This sequence change creates a premature translational stop signal (p.Tyr136*) in the GJB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 91 amino acid(s) of the GJB2 protein. This variant is present in population databases (rs771409330, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with non-syndromic hearing loss (PMID: 30168495). ClinVar contains an entry for this variant (Variation ID: 1357104). 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: Feb 28, 2024

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