HGVS nomenclature in 2019 

The recommendations for the description of variants in DNA, RNA and protein sequences, HGVS nomenclature, is supported by the Human Genome variation Society (HGVS), Global Variome/Human Variome Project (GV/HVP) and the Human Genome Organisation (HUGO). In 2019 the Sequence Variant Description working group (SVD-WG), the committee authorising the nomenclature, was extended with a new member, Peter Causey-Freeman (Leicester, UK). The SVD-WG completed Community Consultation calls for SVD-WG007 (RNA fusion) and SVD-WG008 (RefSeq) suggesting changes to the nomenclature. Other proposals are in preparation, incl. deletion-insertions, repeated sequences and HGVS/ISCN. End of 2018 HGVS version 19.01 was released (replacing version 15.11). The SVD-WG did not release a new version in 2019. Johan den Dunnen, representing the SVD-WG, participated in the ISCN meeting (Copenhagen, Denmark) preparing the new ISCN2020 version. 

The SVD-WG chair, Johan den Dunnen (Leiden, NL), received ~220 questions about HGVS nomenclature (e-mail and facebook) all of which have been answered. Based on the questions received, 17 facebook posts were made, mirrored on the HGVS twitter. Mostly triggered by questions or remarks received, a range of improvements were made to the HGVS nomenclature website (vArnomen.hgvs.org), correcting errors, adding examples and improving explanation. 

HGVS nomenclature website usage increased from ~400 to ~500 visitors daily (peaking at 650). The 2019 annual total was 154,000 sessions. (121,000 in 2018). 

HGVS nomenclature presentations were given at several national and international meetings / courses / workshops in Nederland, France (Paris), Russia (Moscow), Korea (Seoul) and Denmark (Copenhagen). 

In 2019 the HGNC was delighted to announce our 40th anniversary. The first full human gene nomenclature guidelines were published in 1979, following discussions at the Human Genome Meeting in Edinburgh, Scotland that year. We are proud to be able to call ourselves one of the longest standing biocuration projects and look forward to taking the project into its fifth decade. 

Additions to our website (www.genenames.org) in 2019 included a new public “curator notes” field to our Symbol Reports, which allows us to add free text to our Reports to clarify certain aspects of the symbol, name or locus type. We further added a new “stable symbol” tag to nearly 2,000 selected symbols on our Report pages, to signify that these are symbols we have manually checked and have no intention of ever changing. This is in response to requests from the clinical community for more stability in gene nomenclature wherever possible. However, some changes are necessary – for example, we also updated the highly problematic set of symbols that were automatically being converted to dates in Microsoft Excel so that this will no longer happen. We also withdrew all approved symbols that had been assigned to the locus type “phenotype only”, as this work has been passed on to our colleagues at OMIM. 

Our sister project, the Vertebrate Gene Nomenclature Committee (VGNC) assigns standardized nomenclature for vertebrate species that lack their own nomenclature committees. In 2019, in addition to naming chimp, dog, cow and horse genes we added macaque and cat to the set of species that we are currently naming. We also updated the VGNC website to enable the release of new gene family data, initially for the complex cytochrome P450 gene family in primates. 

The BRCA Exchange team at the UC Santa Cruz Genomics Institute is proud to announce the development of a CDH1 Exchange variant portal, through the support of the patient advocacy nonprofit "No Stomach For Cancer". Stomach cancer is the fifth most common type of cancer worldwide, with over 1 million new cases per year globally and 28,000 within the U.S.  Stomach cancer is also deadly, with an average survival five-year survival rate of 29.3%, as it is typically detected in later stages when it has already spread to nearby tissues. Hereditary Diffuse Gastric Cancer (HDGC) is a rare subtype of stomach cancer that arises through genetic risk, and has an earlier age of onset and worse prognosis than most stomach cancers.  Yet these cancers are also preventable. HDGC arises through inherited mutations in a number of genes, most notably CDH1 (Cadherin 1). While individuals who carry harmful CDH1 mutations have an 80% lifetime risk of stomach cancer, and women who carry these mutations also have a 42% lifetime risk of lobular breast cancer, individuals who carry these mutations can manage this risk through screening and risk-reducing surgeries. However, not every mutation to CDH1 affects individuals’ cancer risks. Identifying those mutations that actually increase the risk of cancer is an active area of research, and one in which the UC Santa Cruz Genomics Institute is proud to participate.