Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation

摘要

BackgroundThe frequency of a variant in the general population is a key criterion used in the clinical interpretation of sequence variants. With certain exceptions, such as founder mutations, the rarity of a variant is a prerequisite for pathogenicity. However, defining the threshold at which a variant should be considered “too common” is challenging and therefore diagnostic laboratories have typically set conservative allele frequency thresholds.