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VIP‐HL: Semi‐automated ACMG/AMP variant interpretation platform for genetic hearing loss
Author(s) -
Peng Jiguang,
Xiang Jiale,
Jin Xiangqian,
Meng Junhua,
Song Nana,
Chen Lisha,
Abou Tayoun Ahmad,
Peng Zhiyu
Publication year - 2021
Publication title -
human mutation
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24277
Subject(s) - medical genetics , interpretation (philosophy) , hearing loss , genomics , computational biology , computer science , biology , genetics , audiology , gene , medicine , programming language , genome
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 Variant Interpretation Platform for genetic Hearing Loss (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 in which 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 at http://hearing.genetics.bgi.com/.