Question Regarding HGVS Nomenclature for Two Close Deletions Detected by NGS

[Hertl Gregor]

Dear Sir/Madam,

we would like to ask for your guidance regarding the correct HGVS nomenclature for a variant detected by NGS analysis.

In a tumor sample, NGS reported two separate variants:

BRCA2

NM_000059.3:c.3238delG (chr:13-32911729)

NM_000059.3:c.3242delG (chr:13-32911733)

However, based on BAM file inspection, these two deletions appear to occur on the same allele and represent a single complex event rather than two independent mutations, as currently reported by the NGS pipeline.

Could you please advise how these two deletions should be correctly combined and described according to HGVS recommendations?

Thank you very much for your assistance.

Kind regards,

Gregor Hertl, mag. farm.

Department of molecular diagnostics

[Johan den Dunnen]

Dear Gregor,

in cases like this, where two variants on the same allele both affect the reading frame, it is best to describe them as one variant:

NC_000013.11:g.32337593_32337597delinsATT NM_000059.3:c.3238_3242delinsATT p.(Asp1080IlefsTer2).

The alternative is to describe the variant as NC_000013.11:g.[32337593del;32337597del] NM_000059.3:c.[3238del;3242del] p.(Asp1080IlefsTer2).

Please note that HGVS nomenclature demands that all variants are described on the genomic level, descriptions at other level, e.g. transcript level, may be added. In addition, HGVS nomenclature advises using c.3238del, not c.3238delG (containing redundant information).

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op maandag 15 december 2025 om 12:32:38 UTC+1 schreef Hertl Gregor: