hgvs: A Python package for manipulating sequence variants using HGVS nomenclature: 2018 Update

Abstract

The Human Genome Variation Society (HGVS) nomenclature guidelines encourage the accurate and standard description of DNA, RNA, and protein sequence variants in public variant databases and the scientific literature. Inconsistent application of the HGVS guidelines can lead to misinterpretation of variants in clinical settings. Reliable software tools are essential to ensure consistent application of the HGVS guidelines when reporting and interpreting variants. We present the hgvs Python package, a comprehensive tool for manipulating sequence variants according to the HGVS nomenclature guidelines. Distinguishing features of the hgvs package include: (1) parsing, formatting, validating, and normalizing variants on genome, transcript, and protein sequences; (2) projecting variants between aligned sequences, including those with gapped alignments; (3) flexible installation using remote or local data (fully local installations eliminate network dependencies); (4) extensive automated tests; and (5) open source development by a community from eight organizations worldwide. This report summarizes recent and significant updates to the hgvs package since its original release in 2014, and presents results of extensive validation using clinical relevant variants from ClinVar and HGMD.

Whole exome sequencing of a family revealed a novel variant in the CHM gene, c.22delG p.(Glu8Serfs*4), which co-segregated with choroideremia

“…Variants were preferentially selected for further analysis and validation if they met all of the following criteria: (i) minor allele frequency < 0.01 in the 1000 Genomes Project database (http://www.internationalgenome.org/), Exome Aggregation Consortium database (ExAC, http:// exac.broadinstitute.org/), and Genome Aggregation database (gnomAD, http://gnomad.broadinstitute.org/); (ii) occurrence in exon regions or canonical splicing sites that affected RNA splicing; (iii) potential functional effects of nonsynonymous single nucleotide variants were predicted to be damaging or deleterious using multiple lines of computational prediction; (iv) candidate gene variants related to ophthalmic hereditary disease, especially for inherited retinal disease; (v) other reported potential pathogenic variants that did not met the above criteria (e.g., high minor allele frequency variants, deep-intronic variants, and synonymous single nucleotide variants). Variant nomenclature complied with the recommendations of the Human Genome Variation Society (HGVS, http://www.hgvs.org/) [24]. Variant annotation complied with the guidelines of the American College of Medical Genetics (ACMG, https://www.acmg.net/) [25,26].…”

Application of targeted exome and whole‐exome sequencing for Chinese families with Stargardt disease

“…The nomenclature used for the variants was in compliance with the recommendations of the Human Genomic Variation Society ([HGVS], http://www.hgvs.org) (Wang et al, 2018). Sequence alignments were performed using the Torrent Suite (Li & Durbin, 2010).…”

SeqRepo: A system for managing local collections biological sequences

“…Furthermore, dependencies on remote services create risks for privacy, reproducibility, and overall system availability. These were the problems for which we developed SeqRepo in 2016 as a component for the hgvs Python package (Wang et al, 2018). Using SeqRepo increases validation and variant projection throughput by nearly 50-fold relative to remote sequence access.…”