Question Regarding HGVS Nomenclature

[김훈석]

Dear HGVS Committee,

I hope this message finds you well.

My name is Prof. Hoonseok Kim, and I am a clinical geneticist at Seoul St. Mary's Hospital in South Korea. I have a question regarding the correct application of HGVS nomenclature.

Specifically, I am inquiring about the following variant.

Genomic Level: NM_007294.4(BRCA1):c.922_924delinsT

I think that the protein-level representation is p.(Ser308Ter). However, ClinVar (Accession: VCV000055753.20) lists the protein-level representation as p.Lys307_Ser308insTer.

I have reviewed the recommendations in the "recommendations/protein/delins" section but find it difficult to determine the accurate HGVS nomenclature for this variant. Could you please provide clarification on which representation is correct according to HGVS standards?

I would greatly appreciate your guidance and any additional information you can provide.

Thank you very much for your time and assistance.

Best regards,

Hoonseok Kim

[Johan den Dunnen]

Dear Hoonseok Kim,

to answer your question, please first note that following HGVS nomenclature a correct description of the variant is NM_007294.4:c.922_924delinsT, i.e. without "(BRCA1)". HGVS does not allow the use of gene symbols in variant descriptions.

The predicted consequence on protein level can indeed be described as p.(Ser308Ter), please note the use of "( )" to indicate you give predicted consequences. The description "p.(Lys307_Ser308insTer)" does not follow HGVS nomenclature, see https://hgvs-nomenclature.org/stable/recommendations/general/: "descriptions on RNA/protein level should describe the changes observed on that level (RNA/protein) and not try to incorporate any knowledge regarding the change on DNA-level").

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)
http://www.HGVS.org/varnomen

Op dinsdag 6 augustus 2024 om 06:58:52 UTC+2 schreef 김훈석: