ClinVar

Description

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.