Ensemble and consensus approaches to prediction of recessive inheritance for missense variants in human disease.

ABSTRACT: Mode of inheritance (MOI) is necessary for clinical interpretation of pathogenic variants; however, the majority of variants lack this information. Furthermore, variant effect predictors are fundamentally insensitive to recessive-acting diseases. Here, we present MOI-Pred, a variant pathogenicity prediction tool that accounts for MOI, and ConMOI, a consensus method that integrates variant MOI predictions from three independent tools. MOI-Pred integrates evolutionary and functional annotations to produce variant-level predictions that are sensitive to both dominant-acting and recessive-acting pathogenic variants. Both MOI-Pred and ConMOI show state-of-the-art performance on standard benchmarks. Importantly, dominant and recessive predictions from both tools are enriched in individuals with

SUBMITTER: Petrazzini BO 

PROVIDER: S-EPMC11704621 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature