Question regarding deletions beyond the transcribed region

[Bosscher, L (medgen)]

Dear HGVS committee,

 

We are a diagnostic laboratory from the UMCG (University Medical Center of Groningen) in the Netherlands.

We want to describe the deletions and duplications according to the HGVS Nomenclature general "exon-based" description.

This works well for most duplications/deletions, but we don't know how to describe duplications/deletions that lie outside the transcribed region.

We have attempted to describe the SMN1 deletion exons 7 & 8 using the general "exon-based" description.

We arrive at the following:

(723+1_724-1)_(*1_*4-1) del p.?            NM_000344.4                 GRCH37(hg19).              Systemic numbering

Another example is deletion exons 4 through 10 in the IKBKG gene, which arrives at:

(399+1_400-1)_(*1_*572-1) del p.?       NM_001099857.5          GRCH37(hg19).              Systemic numbering

 

Under the heading "deletions extending beyond the transcribed region," we saw that the HGVS nomenclature committee is discussing whether a c.-based format should be proposed.

We're wondering if you already know more about this.

And if you could help us with the correct HGVS nomenclature of both deletions mentioned here above?

 

Thank you very much in advance,

 

Kind regards,

Laura Bosscher

 

 

 

---

De inhoud van dit bericht is vertrouwelijk en alleen bestemd voor de geadresseerde(n). Anderen dan de geadresseerde(n) mogen geen gebruik maken van dit bericht, het niet openbaar maken of op enige wijze verspreiden of vermenigvuldigen. Het UMCG kan niet aansprakelijk gesteld worden voor een incomplete aankomst of vertraging van dit verzonden bericht.

The contents of this message are confidential and only intended for the eyes of the addressee(s). Others than the addressee(s) are not allowed to use this message, to make it public or to distribute or multiply this message in any way. The UMCG cannot be held responsible for incomplete reception or delay of this transferred message.

[Johan den Dunnen]

Dear Laura,

following current HGVS nomenclature, variants must be described at a genomic level, descriptions at other levels may be added.

- the first variant is described as NC_000005.10:g.(70944754_70946065)_(70951995_70952438)del NM_000344.3:c.(723+1_724-1)_(*3+1_*4-1)del. Note that when you use an "exon-based" description "(*1_*4-1)" is not correct.

- the second variant is described as NC_000023.11:g.(154556377_154558531)_(154565033del_?)del NM_001099857.5:c.(399+1_400-1)_(*572_?)del. Note again that for an "exon-based" description "(*1_*572-1)" can not be used (both position are not flanking an exon). For the description I assumed the 3'end of the deletion extends beyond the reference transcript.

> Under the heading "deletions extending beyond the transcribed region," we saw that the HGVS nomenclature committee 

> is discussing whether a c.-based format should be proposed.

In my reply I assumed the c.format will be allowed for deletions extending beyond the transcribed region.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op dinsdag 27 januari 2026 om 15:10:24 UTC+1 schreef Bosscher, L (medgen):