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bioRxiv · 10.1101/2020.08.10.243642

VIP-HL: Semi-automated ACMG/AMP variant interpretation platform for genetic hearing loss

Peng, J.·Xiang, J.·Jin, X.·Meng, J.·Song, N.·Chen, L.·Tayoun, A. A.·Peng, Z.
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Abstract

PurposeThe 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. MethodsVIP-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. ResultsWe 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). 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 available with a user-friendly web interface at http://hearing.genetics.bgi.com/. ConclusionVIP-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.

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Peng, J., Xiang, J., Jin, X., Meng, J., Song, N., Chen, L., Tayoun, A. A., Peng, Z.. 2020-08-10. VIP-HL: Semi-automated ACMG/AMP variant interpretation platform for genetic hearing loss. https://doi.org/10.1101/2020.08.10.243642

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