Epilepsy-associated CHD2 missense variants and optimization strategies for genetic diagnosis: a comparative analysis of algorithms

BackgroundThe CHD2 gene is one of the most common causative genes of developmental and epileptic encephalopathy (DEE). With the advent of high-throughput sequencing, identifying CHD2 variants has increased, necessitating evaluation of the gene-specific performance of widely used tools, as genome-wide benchmarks may mask such heterogeneity.MethodsThe dataset of pathogenic and control CHD2 missense variants was curated from ClinVar, HGMD, and PubMed databases. Tools included SIFT, SIFT4G, Polyphen