Clarification on HGVS RNA Nomenclature for MET Exon 14 Skipping Variant

[Hannah Masotti]

Hello,

 

I am a Medical Scientist in Molecular Pathology at Peter MacCallum Cancer Centre and would appreciate some clarification regarding the HGVS nomenclature of a MET exon 14 skipping variant at the RNA level.

 

Using our DNA NGS assay, we detected the variant NM_000245.4(MET):c.3028G>C, p.(Leu964_Asp1010del). On our RNA assay, the corresponding event was identified as MET exon 14 skipping. We have routinely described the RNA alteration for this variant as r.2888_3028del. However, when we recently entered the variant into Mutalyzer, the recommended nomenclature was r.2891_3031del. We understand that Mutalyzer has applied the HGVS 3′ rule; however, we are uncertain whether this rule should be applied in this context, given the exception described on the HGVS RNA nomenclature page:

And the exception noted on the HGVS deletion nomenclature page:

Could you please clarify which RNA-level description would be considered correct according to current HGVS recommendations?

 

Any guidance you can provide would be greatly appreciated.

 

Kind regards,

 

Hannah Masotti
Medical Scientist – Molecular Oncology

Molecular Pathology



Phone +61 3 8559 5405 (laboratory enquiries)

Email  Hannah....@petermac.org

 

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[Johan den Dunnen]

Dear Hannah,

following HGVS nomenclature, the variant should be described as NC_000007.14:g.116771989G>C NM_000245.4:c.3028G>C r.(2891_3031del) p.(Leu964_Asp1010del).

Note that HGVS nomenclature does not allow the use of gene symbols in variant descriptions. When desired, you could use "MET NC_000007.14:g.116771989G>C NM_000245.4:c.3028G>C r.(2891_3031del) p.(Leu964_Asp1010del)".

You correctly listed the relevant nomenclature page stating that "the exception to the 3'rule for deletions around exon/exon junctions does not apply when describing variants based on an RNA reference sequence". So correct is r.(2891_3031del) and not r.(2888_3028del). Note I used parentheses since I assume you did not analyze RNA, so give the predicted consequences at the RNA level.

Finally, I noticed you use a "," (comma) to separate descriptions at the coding DNA and protein level. Please note HGVS nomenclature only uses " " (a space).

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op donderdag 4 juni 2026 om 07:52:17 UTC+2 schreef Hannah Masotti: