Nomenclature for Stop-Loss Deletion Variant

[Kerri Smith]

Hi,

We have identified the following variant and are struggling to determine the proper protein nomenclature:

NM_001005242.3(PKP2):c.2510_*1del

chr12:32792422 CCTCAGT > C

This is a 6 bp deletion that results in the loss of the last amino acid in the protein (Asp837), loss of the termination codon, and extension by two amino acids (Gly-Lys) before a new termination codon. The Variant Validator program is unable to provide a protein nomenclature (just p.?) and the Mutalyzer 3 program returns p.(Asp837GlyfsTer3). I at first thought  Mutalyzer to be incorrect as my understanding was that the extension should be prioritized - but reading a previous thread on this forum (https://groups.google.com/g/hgvs-nomenclature/c/2S9Jdcquk_Y/m/wVer8TpCBgAJ) seems to imply that my variant type is not technically an extension because the last amino acid is changed. Nomenclature that only describes the extension doesn't quite seem correct, as it does not also describe loss of Asp837. The closest I could come up with would be p.(Asp837delextTer2), but I've not seen a variant described like this before. Perhaps Mutalyzer is correct? Thank you for any help you can provide!

Kerri Smith

[Johan den Dunnen]

Dear Kerri,

following HGVS nomenclature the variant should be described as NC_000012.12:g.32792425_32792430del NM_001005242.3:c.2510_*1del p.(Asp837GlyfsTer3).

Note that HGVS demands that "all variants should be described at the most basic level, the DNA level. Descriptions on the RNA and/or protein level may be given in addition", see Geneneral recommendations.

Furthermore, HGVS does not allow the addition of gene symbols in variant nomencalture, so "NM_001005242.3(PKP2):c.2510_*1del" should not be used.

As you mention, the variant cannot be described as an "extension" since the last amino acid is changed, the variant is therefore a frame shift (Recommendations > Protein > Frame shift: "deletions starting 5' of and including the translation termination (stop) codon are described as frameshift"). 

When I tried, both VariantValidator and Mutalyzer give "p.(Asp837GlyfsTer3)" as the predicted consequences at protein level.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op dinsdag 2 juni 2026 om 17:29:22 UTC+2 schreef kerris...@gmail.com: