HGVS nomenclature Query - insertions at RNA level

[Nick]

Hi there,

We have recently identified the below insertion and was wondering if we could please check if the nomenclature is correct according to HGVS? 

The genomic variant we assessed at RNA level which was: NM_130838.1 UBE3A  c.2294G>C which is in the last base of the exon. 

We found two intronic insertions associated with this variant: r.2294_2295ins2294+1_2294+45 and r.2294_2295ins2294+1_2294+78

We can also see the r.2294g>c at the RNA level. 

Can we incorporate all 3 findings in one nomenclature? We were thinking possible options could be: 

r.[2294g>c;2294_2295ins[2294+1_2294+45,2294+1_2294+78]] or r.2294delins[c;2294+1_2294+45,c;2294+1_2294+78]

At protein level we predict p.(Arg765ThrTer) and wondered if the correct HGVS nomenclature would be: p.(Arg765ThrfsTer2)

Many thanks in advance for your help

Nick 

[Johan den Dunnen]

Dear Nick,

following HGVS nomenclature, I get to NC_000015.10:g.25354353C>G NM_130838.1:c.2294G>C r.[2294delins[C;c.2294+1_2294+45],2294delins[C;c.2294_2295ins2294+1_2294+78]] p.Arg765ThrfsTer2

Note HGVS nomenclature demands that a description at genomic level is mandatory (NC_000015.10:g.25354353C>G). I also follow upcoming updates of the nomenclature correcting the use of upper-case nucleotide descriptions at RNA level (following IUPAC standards) and the addition of "c." to refer to the origing of intronic insertions.

I used the "delins" format since the description you get is shorter. Still, for the variant at RNA level you can also use r.[[2294G>C;2294_2295ins[c.2294+1_2294+45]],[2294G>C;2294_2295ins[c.2294_2295ins2294+1_2294+78]]].

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op vrijdag 19 december 2025 om 13:39:56 UTC+1 schreef Nick:

[Nick]

Great, thank you so much! 

BW. 

Nick