Fig. 2: Workflow.

Our workflow began with creating cohorts within the datasets. We leveraged short-read whole genome sequencing data to characterize genes of interest. Variant annotation focused on missense, frameshift, start loss, stop loss, stop gain, and splicing variants. Next, we compared the frequency of identified variants in cases and controls. Pathogenicity assessment involved 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 prioritized variants that were present only in the case cohort and had a CADD score greater than 20.