Systematic evaluation of gene variants linked to hearing loss based on allele frequency threshold and filtering allele frequency.

ABSTRACT: As the number of genes identified for linkage to hearing loss has been increasing and more public databases have become available, we aimed to systematically evaluate all variants reported for nonsyndromic hearing loss (NSHL) based on their allele frequencies (AFs) in the general population. Among the 3,549 variants in 97 NSHL genes reported as pathogenic/likely pathogenic in ClinVar and HGMD, 1,618 were found in public databases (gnomAD, ExAC, EVS, and 1000G). To evaluate the pathogenicity of these variants, we employed AF thresholds and NSHL-optimized ACMG guidelines. AF thresholds were determined using a high-resolution variant frequency framework and Hardy-Weinberg equilibrium calculation: 0.6% and 0.1% for recessive and dominant genes, respectively. Filtering AFs of variants linked to

SUBMITTER: Rim JH 

PROVIDER: S-EPMC6418148 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature