Skip to main content
Posted by on in News
GV Newsletter - December 2021


More information, please visit:
One activity of HVP/GV that has continued under the new organization of HUGO is a working group of Genetics Journals Editors. Chaired by Garry Cutting (Human Mutation), the group meets monthly online to discuss topics of mutual interest. A key focus has been the adoption of HGVS nomenclature for variant descriptions in all publications. As a first step, the group conducted a pilot study to evaluate the workload imposed by requiring authors to verify variant compliance with HGVS nomenclature using public software. The two primary software tools are Mutalyzer and Variant Validator.  Editorial staff at Human Genetics and Genetics in Medicine conducted the pilot and reporting that the burden of variant validation to editorial staff to editorial staff was minimal. 

Earlier this year the group published their result along with guidelines for implementing variant validation: Higgins et al. (2020). Verifying nomenclature of DNA variants in submitted manuscripts: Guidance for journals. Hum Mutat. 2021 42: 3-7 (">

The manuscript recommends that journals require authors check variant descriptions using online tools like Mutalyzer ( or Variant Validator ( One metric to evaluate adoption of these guidelines is traffic at the websites that offer variant validation tools. The Mutalyzer team shared the the figure below. Based on unique IP addresses the number of monthly variant check requests nearly tripled when the Guidelines paper was published online. 

The Variant Validator group reported that prior to December 2019, the batch analysis was only being used sporadically. Since the Pilot Project, we are seeing above 500 users a month at least, and since the paper was released, this has increased to around 800-1000 users a month.
These are remarkable results, illustrating that journals can be instrumental in the adoption of genomics standards that improve the quality of variant data published.


HUGO Gene Nomenclature Committee recommendations for the designation of gene fusions

The HUGO Gene Nomenclature Committee (HGNC) has recently published a new recommendation that fusion genes be designated using a double colon (e.g.BCR::ABL) (Bruford et al., 2021). Fusion genes are a common feature in the causation of particular tumour types, and can arise as a consequence of reciprocal translocations, such as are seen in Burkitt lymphoma (BL) and in chronic myeloid leukaemia (CML). CML is now known to result from the creation of a fusion gene, at the breakpoint, comprising the 5′ part of the BCR gene at 22q11 with the 3′ part of the ABL1 tyrosine kinase-encoding gene from 9q34. The abnormal protein expressed from this fusion gene displays increased tyrosine kinase activity. To date, almost 1000 gene fusions have been found by genomic characterization of breakpoints in cytogenetically identified aberrations, balanced as well as unbalanced, in various leukaemias, lymphomas, and solid tumours.

There has never been a generally recommended, standardised way to denote gene fusions. Instead, multiple notations have been used with varying popularity over time, the most common designation being SYMBOL-SYMBOL, followed by SYMBOL/SYMBOL. However, both designations have shortcomings. Hyphens are already used in the designation of readthrough transcripts (e.g.INS-IGF2), of members of protein complexes (e.g., MRE11-RAD50-NBN), or within some gene symbols (e.g.TRX-CAT1-2). Similarly, the forward slash is used by the International System for Human Cytogenomic Nomenclature (ISCN) to denote different clones, both constitutionally (mosaicism) and in cancer cells, and the Human Genome Variation Society (HGVS) guidelines also use a forward slash to indicate mosaicism. It is also used in the literature in place of “either/or” (e.g.BRCA1/2), to denote involvement of alternative genes in a fusion (e.g.SS18-SSX1/SSX2), and in pathway and complex descriptions (e.g., RAS/RAF/MAPK).

To avoid further potential confusion arising from the multiple possible meanings of hyphens and forward slashes, HGNC consulted with a group of experts and proposed the use of a double colon (::). which denotes break and reunion in ISCN nomenclature, and was first established in the HGVS variant guidelines to indicate transcript fusions.
This new standard has already attracted attention from others, with one group proposing future extensions to the standard (Wagner et al., 2021) and the authors of a new review on round cell sarcomas having embraced the new standard (Kallen and Hornick, 2021).



  • Bruford EA, Antonescu CR, Carroll AJ, Chinnaiyan A, Cree IA, Cross NCP, et al. (2021) HUGO Gene Nomenclature Committee (HGNC) recommendations for the designation of gene fusions. Leukemia, 35:3040-3043. DOI: 10.1038/s41375-021-01436-6

  • Kallen ME, Hornick JL (2021) From the ashes of "Ewing-like" sarcoma: A contemporary update of the classification, immunohistochemistry, and molecular genetics of round cell sarcomas. Semin Diagn Pathol, published online ahead of print. DOI: 10.1053/j.semdp.2021.10.002

  • Wagner AH, Akkari Y, Li M, Roy A, Tsuchiya K, Raca G (2021) Recommendations for future extensions to the HGNC gene fusion nomenclature. Leukemia, published online ahead of print. DOI: 10.1038/s41375-021-01458-0

HGVS nomenclature Q&A 
The third HGVS nomenclature online Q&A session took place on November 9th.  Not many participants were present live, but it was still an entertaining session. Johan den Dunnen posted questions on HGVS nomenclature which participants answered using the DirectPoll platform. As in previous sessions, no participant was able to answer all questions correctly.
Want to give it a try?  The questions are available on Socrative (, classroom HGVSonline3). 
Joining live is much more fun: the next online Q&A session will be on January 11, 3pm GMT. Want to join? Please register:
One of the questions was:
           Who knows variant NC_045512.2:g.23604C>G?  What is it?
           Do you know? (for the right answer see the end of the Newsletter)

If you have any comments, suggestions or questions you would like answered for these sessions, please let us know. 
Interested to support the HGVS nomenclature work? Please consider sponsoring one of the bi-monthly meetings. For details, please contact"> Of course, we will acknowledge sponsorship in advertisement and during the meeting.


UCSC researchers double-down on data sharing’s key role in global health 

Scientists present framework for freely and safely sharing health data on a global scale in a brand new, open access journal 

Titled “" target="_blank" rel="noopener" style="color: rgb(38, 171, 226); font-weight: normal; text-decoration: underline;" title="mailto:">GA4GH: International policies and standards for data sharing across genomic research and healthcare,” first author and GA4GH vice-chair Heidi Rehm and GA4GH community co-authors present the organization’s strategies for addressing some of the most pressing challenges of the genomic data revolution. The authors present the GA4GH toolkit of secure, interoperable technical standards and policy frameworks, their relevance to key domains of research and clinical care, and the organization’s future plans. 

Genomics Institute and Baskin Engineering Associate Research Scientist Melissa Cline, who is a GA4GH Steering Committee member and GA4GH Driver Project Champion for the BRCA Challenge, was co-author on the showcase paper, which provides a high-level overview of the GA4GH organization, deliverables, and strategy for enabling interoperability across the international genomics landscape. Dr. Cline is also a co-author on the commentary article “" target="_blank" rel="noopener" style="color: rgb(38, 171, 226); font-weight: normal; text-decoration: underline;">International federation of genomic medicine databases using GA4GH standards” and the technology article "" target="_blank" rel="noopener" style="color: rgb(38, 171, 226); font-weight: normal; text-decoration: underline;">The GA4GH Variation Representation Specification: A computational framework for variation representation and federated identification”, and one of the GA4GH contributors featured in “" target="_blank" rel="noopener" style="color: rgb(38, 171, 226); font-weight: normal; text-decoration: underline;">Voices of GA4GH members: Collaborating in technology and policy development”.

Announcing GA4GH Special Issue in Cell Genomics
This issue is the culmination of an incredible effort from the global GA4GH contributor community and includes ten papers. “The entire GA4GH community has come together across time and space to deliver the resources described in this special issue,” said GA4GH CEO Peter Goodhand. “It represents an important milestone in the evolution of this organization.”
Read GA4GH Press Release
Read GA4GH Special Issue

We welcome you to the 14th International Congress of Human Genetics (ICHG2023) to be held in Cape, South Africa, proudly hosted by the African Society of Human Genetics (AfSHG) and the Southern African Society for Human Genetics (SASHG).
Taking into account the COVID-19 pandemic, we are formally sharing the news that the ICHG will be postponed to 22-26 February, 2023. 
Warm regards
Raj Ramesar and Charles Rotimi
(Co-Chairs LOC/ICHG 2023)

HGVS nomenclature Q&A 

The question was:
           Who knows variant NC_045512.2:g.23604C>G?  What is it?
           Do you know? (for the right answer see the end of the Newsletter)

[ Variant NC_045512.2:g.23604C>G is the most discussed variant in 2021, 
it is the SARS-CoV-2 delta variant. ]

This email was sent to 
why did I get this?    unsubscribe from this list    update subscription preferences 
Human Variome Project · Centre for Life · Times Square · Newcastle Upon Tyne, Tyne and Wear NE1 4EP · United Kingdom">Email Marketing Powered by Mailchimp


  • No comments made yet. Be the first to submit a comment

Leave your comment

Don't forget to log in! If you're a member of the Human Variome Project Consortium, you might want to log in before posting a comment. Not a member? Why not sign up?
Guest Wednesday, 27 September 2023