VIP-HL

Semi-automated ACMG/AMP variant interpretation platform for genetic hearing loss. The American College of Medical Genetics and Genomics, and the Association for Molecular Pathology (ACMG AMP) have proposed a set of evidence-based guidelines to support sequence variant interpretation. The ClinGen hearing loss expert panel (HL-EP) introduced further specifications into the ACMG AMP framework for genetic hearing loss. This study aimed to semi-automate the HL ACMG AMP rules. Methods VIP-HL aggregates information from external databases to automate 13 out of 24 ACMG AMP rules specified by HL-EP, namely PVS1, PS1, PM1, PM2, PM4, PM5, PP3, BA1, BS1, BS2, BP3, BP4, and BP7. Results We benchmarked VIP-HL using 50 variants where 83 rules were activated by the HL expert panel. VIP-HL concordantly activated 96% (80 83) rules, significantly higher than that of by InterVar (47%; 39 83)