A Novel Phenotype-based Approach for Prioritizing Candidate Genetic Variants for Autism Spectrum Disorder.

Purpose: Autism spectrum disorder (ASD) is genetically and phenotypically heterogeneous condition, complicating identification of causal variants. Current diagnostic approaches, have limited diagnostic yield, underscoring the need for new strategies. Methods: We developed a phenotype-driven framework to prioritize ASD-associated genetic variants using comprehensive phenotypic and exome sequencing (ES) data from 125 children with ASD. We used the Human Phenotype Ontology (HPO) nomenclature to prioritize candidate variants in each child based on the similarity between its observed phenotypes and variant-specific expected phenotypes. Results: We identified 228 HPO terms grouped into 41 phenotyp