VarGrouper: A Bioinformatic Tool for Local Haplotyping of Deletion–Insertion Variants from Next-Generation Sequencing Data after Variant Calling

Publication date: Available online 20 February 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Ryan J. Schmidt, Allison Macleay, Long Phi LeAccurate genetic variant representation through nomenclature and annotation is essential for understanding functional consequence and properly noting the presence of variants across time, assays, and laboratories. Current variant calling algorithms detect single deletion–insertion variants as multiple indel and/or substitution variants from next-generation sequencing data. Consequently, these variants are separately annotated in bioinformatics pipelines, leading to inaccurate variant representation. We developed a bioinformatic solution to this problem—VarGrouper—that automatically recognizes individual variants that arise from a deletion–insertion variant and aggregates them into a single variant that can be properly annotated. This tool has been integrated into our routine clinical molecular diagnostics workflow for DNA sequencing of solid tumors. Over an 11-month period, VarGrouper variants were reported by all attending molecular pathologists involved in interpretation and represented 4.1% of all variants reported; 10.9% of cases with reportable variants contained at least one VarGrouper variant. VarGrouper improves the practice of molecular diagnostics by increasing the accuracy and consistency of variant annotation. VarGrouper is freely available for use by the molecular diagnostic community.

Source: The Journal of Molecular Diagnostics - March 13, 2019 Category: Pathology Source Type: research