VarGrouper

Abstract

Accurate 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 deletioneinsertion 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 problemdVarGrouperdthat automatically recognizes individual variants that arise from a deletioneinsertion 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.