ClinVar

Description

The His100fs variant in GJB2 has been previously reported in several individuals with hearing loss who were homozygous or compound heterozygous (Abe 2000, Bayazit 2003, Gabriel 2001, Park 2000, Snoeckx 2005, Wang 2002, Zhang 2010, LMM unpublished data). This variant has also been identified in 0.09% (18/19950) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). This frameshift variant is predicted to alter the protein’s amino acid sequence beginning at position 100 and lead to a premature termination codon 14 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the GJB2 gene is an established disease mechanism in autosomal recessive hearing loss. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PVS1, PM3, PM2_Supporting.