RESUMO
Human Genome Variation Society (HGVS) nomenclature is a de facto clinical standard for reporting DNA sequence variants. With increasing use of high-throughput sequencing, manual generation of HGVS nomenclatures for all variants is impractical and error-prone. It is therefore beneficial to include one or more HGVS generator tools in next-generation sequencing (NGS) bioinformatics pipelines to enable automated, consistent, and accurate generation of HGVS nomenclature after appropriate validation. The authors implemented an HGVS nomenclature tool, the hgvs package, by integrating it into their custom-developed NGS variant management and reporting software. Use of Docker containers provided a strategic advantage to the integration process. Clinical implementation of the hgvs package was validated using a cohort of 330 variants that appropriately represented cancer-related genes and clinically important variant types. The hgvs package was able to generate HGVS-compliant variant nomenclature (both c. and p.) for 308 of the 330 (93.3%) variants, including all those in the coding and untranslated regions, and 32 of 35 (91.4%) in the consensus splice site region. Discrepant HGVS nomenclature involved variants in the intronic (16 of 40) and consensus splice site (3 of 35) regions with repeat sequences. Overall, implementation of the hgvs package in the clinical NGS workflow improved consistency and accuracy of reporting HGVS nomenclature.
