Figure 2-. Workflow.

Our workflow begins with creating cohorts within the datasets. We leverage short-read whole genome sequencing data to characterize genes of interest. Variant annotation focuses on missense, frameshift, start loss, stop loss, stop gain, and splicing variants. Next, we compare the frequency of identified variants in cases and controls. Pathogenicity assessment involves using ClinVar, Human Gene Mutation Database (HGMD), American College of Medical Genetics and Genomics (ACMG) guidelines, and Combined Annotation Dependent Depletion (CADD) scores. Finally, we prioritize variants that are present only in the case cohort and have a CADD score greater than 20.