loading page

VIP-HL: Semi-automated ACMG/AMP variant interpretation platform for genetic hearing loss
  • +5
  • Jiguang Peng,
  • Jiale Xiang,
  • Xiangqian Jin,
  • Junhua Meng,
  • Nana Song,
  • Lisha Chen,
  • Ahmad Abou Tayoun,
  • Zhiyu Peng
Jiguang Peng
BGI Genomics
Author Profile
Jiale Xiang
BGI Genomics
Author Profile
Xiangqian Jin
BGI Genomics
Author Profile
Junhua Meng
BGI Genomics
Author Profile
Nana Song
BGI Genomics
Author Profile
Lisha Chen
BGI Genomics
Author Profile
Ahmad Abou Tayoun
Al Jalila Children's Specialty Hospital
Author Profile
Zhiyu Peng
BGI Genomics
Author Profile

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 83 rules were activated by the ClinGen HL-EP. VIP-HL concordantly activated 96% (80/83) rules, significantly higher than that of by InterVar (47%; 39/83). Of 4948 ClinVar star 2+ variants from 142 deafness-related genes, VIP-HL achieved an overall variant interpretation concordance in 88.0% (4353/4948). 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/.

Peer review status:UNDER REVIEW

25 Nov 2020Submitted to Human Mutation
01 Dec 2020Submission Checks Completed
01 Dec 2020Assigned to Editor
04 Dec 2020Reviewer(s) Assigned
11 Jan 2021Review(s) Completed, Editorial Evaluation Pending
23 Jan 2021Editorial Decision: Revise Major
19 Mar 20211st Revision Received
23 Mar 2021Submission Checks Completed
23 Mar 2021Assigned to Editor
23 Mar 2021Reviewer(s) Assigned
30 Mar 2021Review(s) Completed, Editorial Evaluation Pending
27 Apr 2021Editorial Decision: Revise Minor
23 May 20212nd Revision Received
25 May 2021Submission Checks Completed
25 May 2021Assigned to Editor
26 May 2021Reviewer(s) Assigned