ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.11del (p.Gly4fs) (rs1555342014)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000588025 SCV000698226 likely pathogenic Deafness, autosomal recessive 1A 2016-04-05 criteria provided, single submitter clinical testing Variant summary: This GJB2 c.11delG variant causes a frameshift, which alters the proteins amino acid sequence beginning at position 4 and leads to a premature termination codon nine amino acids downstream. Mutation taster predicts this variant to be disease-causing. The variant was not observed in the large and broad cohorts of the ExAC project or ESP. The variant of interest was reported in 2 patients with hearing loss (Putcha_GenMed_2007, Banjara_IJOHNS_2015). Truncations downstream of this position have been classified as disease/pathogenic variants by our laboratory such as c.19C>T (p.Gln7X ), c.35dupG (V13fs), and c.35delG (G12fs). Deafness variation database lists the variant as "pathogenic." Considering all evidence, this variant has been classified as Likely Pathogenic until additional information becomes available.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002185 SCV001160056 pathogenic not specified 2018-10-21 criteria provided, single submitter clinical testing The GJB2 c.11delG; p.Gly4fs variant, also published as 8delG, is reported in the medical literature in at least two individuals with hearing loss (Banjara 2016, Putcha 2007). The variant is reported in the ClinVar database (Variation ID: 496214), but is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, the variant is classified as pathogenic in the Deafness Variation Database (see link below) and other frameshift variants in this region are classified as pathogenic (see link to ClinVar below). Considering available information, this variant is classified as pathogenic. References: Link to Deafness Variation Database: http://deafnessvariationdatabase.org Link to GJB2 in ClinVar: http://www.ncbi.nlm.nih.gov/clinvar/?term=GJB2%5Bgene%5D Banjara H et al. Detection of Connexion 26 GENE (GJB2) Mutations in Cases of Congenital Non Syndromic Deafness. Indian J Otolaryngol Head Neck Surg. 2016 Jun;68(2):248-53. Putcha GV et al. A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort. Genet Med. 2007 Jul;9(7):413-26.

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