HGVS Nomenclature 2024: improvements to community engagement, usability, and computability

Abstract

Background: The Human Genome Variation Society (HGVS) Nomenclature is the global standard for describing and communicating variants in DNA, RNA, and protein sequences in clinical and research genomics. This manuscript details recent updates to the HGVS Nomenclature, highlighting improvements in governance, community engagement, website functionality, and underlying implementation of the standard.

Methods: The HGVS Variant Nomenclature Committee (HVNC) now operates under the Human Genome Organization (HUGO), facilitating broader community feedback and collaboration with related standards organizations. The website has been redesigned using modern documentation tools and practices. The specification was updated to include guidance for transcript selection and to align with recent cross-consortia recommendations for the representation of gene fusions. A formal computational grammar was introduced to improve the precision and consistency of variant descriptions.

Results: Major improvements in HGVS Nomenclature v. 21.1 include a redesigned website with enhanced navigation, search functionality, and mobile responsiveness; a new versioning policy aligned with software management practices; formal mechanisms for community feedback and change proposals; and adoption of Extended Backus-Naur Form (EBNF) for defining syntax. The specification now recommends MANE Select transcripts where appropriate and includes updated guidance for representing adjoined transcripts and gene fusions. All content is freely available under permissive licenses at hgvs-nomenclature.org.

Conclusions: These advancements establish a more sustainable foundation for maintaining and evolving the HGVS Nomenclature while improving its accessibility and utility. The introduction of formal computational grammar marks a crucial step toward unambiguous variant descriptions that can be reliably processed by both humans and machines. Combined with enhanced community engagement mechanisms and improved guidance, these changes position the HGVS Nomenclature to better serve the evolving needs of clinical and research genomics while maintaining the stability that users require.

Keywords: Bioinformatics; Clinical genomics; HGVS; Sequence variation; Standards.

Fig. 1

a The landing page for hgvs-nomenclature.org shows the “foldable” navigation menu on the left, a search bar with a clear indication of the selected version, and the Read the Docs version selector to navigate to other versions. The version selector is minimized and unobtrusive by default but expanded here to show functionality. b Mobile version of the landing page. The navigation menu, search features, and selected version are hidden in the “hamburger menu” denoted by the ≡ symbol

Fig. 2

The release notes page provides details of every change to the website since the previous version

Fig. 3

a Syntax for a DNA substitution from the previous website [24]. b Syntax for a DNA substitution from the updated website [25]. The new presentation clarifies that there are two distinct forms of a DNA substitution variant and includes an explanation of the syntactic components of each form

Fig. 4

An excerpt of the new HGVS Syntax Summary pages [26]. The HGVS Syntax Summary shows all syntax rules in HGVS, organized primarily by variant type and secondarily by molecule type. This organization complements that of the website and facilitates readers to compare syntax rules. The syntax rules in the summary and molecule-specific page (Fig. 3b) are drawn from the same file, thereby guaranteeing consistency between these two views