Abstract
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 developed a tool named VIP-HL, aiming to semi-automate the HL ACMG/AMP rules. 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. We benchmarked VIP-HL using 50 variants where 82 rules were activated by the ClinGen HL-EP. VIP-HL concordantly activated 93% (76/82) rules, significantly higher than that of by InterVar (48%; 39/82). VIP-HL is an integrated online tool for reliable automated variant classification in hearing loss genes. It assists curators in variant interpretation and provides a platform for users to share classifications with each other. VIP-HL is available with a user-friendly web interface athttp://hearing.genetics.bgi.com".
| Original language | English |
|---|---|
| Journal | Human Mutation |
| Volume | 42 |
| Issue number | 12 |
| Pages (from-to) | 1567-1575 |
| Number of pages | 9 |
| ISSN | 1059-7794 |
| DOIs | |
| Publication status | Published - 2021 |
Keywords
- Genetic hearing loss
- Variant interpretation
- Bioinformatics
- Clinical genomics