HGVS Nomenclature in Practice: An Example from the United Kingdom National External Quality Assessment Scheme

Abstract

ABSTRACT:The recommendations for the description of sequence variants from the Human Genome Variation Society (HGVS) were published in 2000. Over the years, the recommendations became widely adopted, especially in human clinical genetics and DNA laboratory reporting. As part of a testing scheme performed by the United Kingdom National External Quality Assessment Scheme (UK NEQAS) for Molecular Genetics, we assessed the current variability in the use and interpretation of the guidelines by diagnostic laboratories based across the globe. Twenty-six participating laboratories gave 21 different descriptions. Six laboratories gave fully compliant HGVS descriptions, 12 laboratories reported the correct variant, although not using the recommended format, whilst eight laboratory reports (31%) were not correct. The results indicate that available tools to check variant descriptions were not used. We conclude that education appears to be the way forward to eliminate the observed variability in data reporting. Hum Mutat 37:576-578, 2016. C 2016 Wiley Periodicals, Inc.

Infectious Enthusiasm! Larger than Life! That Laugh! That Smile! In Loving Memory of Richard G.H. (Dick) Cotton

“…He established the Human Genome Variation Society and the HVP as vehicles to bring together interested parties around mutation detection and data sharing, with this journal as the affiliated society journal. And with major efforts not only from Dick, but from other colleagues such as Stylianos Antanorakis, Johan den Dunnen, and many others, an HGVS mutation nomenclature, the present day de facto international standard for clinical genetics, emerged [Deans et al, 2016], while the HVP is working closely with the Global Alliance for Genomics and Health to establish the next generation of genomics standards ad data sharing tools. Some informaticians new to the field may find the HGVS nomenclature system, which is not necessarily rooted in genomic coordinates (although it can be), a little obscure.…”

VariantValidator: Accurate validation, mapping, and formatting of sequence variation descriptions

“…The Human Genome Variation Society (HGVS) nomenclature for the description of human sequence variants (den Dunnen et al., ) is widely adopted by scientific journals and variant databases and is endorsed by professional organizations (Deans, Fairley, den Dunnen, & Clark, ; Richards et al., ; Tack, Deans, Wolstenhome, Patton, & Dequeker, ). As high‐throughput sequencing has become more common, HGVS recommendations have evolved to communicate a plethora of new variants to the scientific and healthcare communities (Taschner & den Dunnen, ).…”

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

“…With the widespread adoption of high‐throughput sequencing and the complexity of DNA, RNA, and protein variants, the HGVS nomenclature has continued to evolve (den Dunnen et al., ). Manually generated HGVS representations are prone to applying HGVS nomenclature guidelines incompletely or incorrectly, resulting in malformed representations, incorrect reference bases or incorrect normalization as required by the HGVS nomenclature (Deans, Fairley, den Dunnen, & Clark, ; Tack et al., ). It is challenging for researchers to manually check all the guidelines in the HGVS nomenclature for each variant discovered in modern sequencing‐based studies.…”

“…Manually generated HGVS representations are prone to applying HGVS nomenclature guidelines incompletely or incorrectly, resulting in malformed representations, incorrect reference bases or incorrect normalization as required by the HGVS nomenclature (Deans, Fairley, den Dunnen, & Clark, 2016;Tack et al, 2016).…”