HGVS nomenclature of DNA and cDNA level

[Yahya Yozbatıran]

Dear Officials,

Dear Officials,

I identified a GCAT insertion at the genomic level: NC_000023.11:g.40073707_40073708insGCAT, which I named accordingly. Upon cDNA sequencing, the same insertion was observed at the transcript level: NC_000023.11(NM_001123385.2):c.1637_1638insGCAT. I would like to confirm if this nomenclature is correct.

I noticed in your examples (Simple DNA Insertions) that the nucleotide sequence at the coding sequence is represented as the reverse complement, e.g., NC_000023.10:g.32862923_32862924insCCT (LRG_199t1:c.240_241insAGG). Could you please clarify the correct way to name my insertion at the cDNA level?

Thank you for your guidance.

Best regards
Yahya Yozbatiran

[Johan den Dunnen]

Dear Yahya,

regarding the variant you give, first the description NC_000023.11:g.40073707_40073708insGCAT does not follow HGVS nomenclature. Correct is NC_000023.11:g.40073706_40073709dup (checked it with both Mutalyzer and VariantValidator).

Second, when you have detected the same insertion on RNA level, the description is NC_000023.11:g.40073706_40073709dup NM_001123385.2:c.1638_1641dup r.1638_1641dup p.Gly548HisfsTer10.

For variant a variant shifted one nucleotide you would get NC_000023.11:g.40073706_40073707insGCAT NM_001123385.2:c.1639_1640insATGC. Indeed, when the gene is on the minus strand, the inserted sequence is described as the reverse complement.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op maandag 1 december 2025 om 14:22:24 UTC+1 schreef yozbati...@gmail.com: