AutoGVP: a dockerized workflow integrating ClinVar and InterVar germline sequence variant classification

Jung Kim; Ammar S Naqvi; Ryan J Corbett; Rebecca S Kaufman; Zalman Vaksman; Miguel A Brown; Daniel P Miller; Saksham Phul; Zhuangzhuang Geng; Phillip B Storm; Adam C Resnick; Douglas R Stewart; Jo Lynne Rokita; Sharon J Diskin

doi:10.1101/2023.11.29.569103

AutoGVP: a dockerized workflow integrating ClinVar and InterVar germline sequence variant classification

bioRxiv [Preprint]. 2023 Dec 1:2023.11.29.569103. doi: 10.1101/2023.11.29.569103.

Authors

Jung Kim¹, Ammar S Naqvi^{2

3}, Ryan J Corbett^{2

3}, Rebecca S Kaufman^{4

5}, Zalman Vaksman^{4

5}, Miguel A Brown^{2

3}, Daniel P Miller^{2

3}, Saksham Phul^{2

3}, Zhuangzhuang Geng^{2

3}, Phillip B Storm^{2

3}, Adam C Resnick^{2

3}, Douglas R Stewart¹, Jo Lynne Rokita^{2

3}, Sharon J Diskin^{4

5

6}

Affiliations

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
² Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA.
³ Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA.
⁴ Department of Bioinformatics and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA.
⁵ Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.
⁶ Department of Pediatrics, University of Pennsylvania, Philadelphia, PA.

Abstract

With the increasing rates of exome and whole genome sequencing, the ability to classify large sets of germline sequencing variants using up-to-date American College of Medical Genetics - Association for Molecular Pathology (ACMG-AMP) criteria is crucial. Here, we present Automated Germline Variant Pathogenicity (AutoGVP), a tool that integrates germline variant pathogenicity annotations from ClinVar and sequence variant classifications from a modified version of InterVar (PVS1 strength adjustments, removal of PP5/BP6). This tool facilitates large-scale, clinically-focused classification of germline sequence variants in a research setting.

Publication types

Preprint

Abstract

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