Complex inversion nomenclature help

[Laura Cobbold]

Dear HGVS team,

 

I was hoping to ask your advice on a complex rearrangement we have identified via diagnostic discovery and are presenting next week so would like a consensus on the nomenclature. The variant is described as:

 

“Complex rearrangement with inverted segment chr2:165998456-210243077 inverted and adjacent to chr2:164374089. chr2:164374089-165998456 in correct orientation after inverted segment. Breakpoint in intron 25 of SCN1A, with regions up and downstream of breakpoint separated”

 

So the inverted segment is moved from one location to one upstream. Our team has come up with the following possibilities but we are unsure:

 

seq[GRCh38]chr2:g.164374088_164374089delins [165998456_210243077inv]

or

seq[GRCh38]chr2:g.165998456_210243077del;164374088_164374089ins[165998456_210243077inv]

 

Any help would be gratefully received

Best wishes

Laura

 

Laura Cobbold

Clinical Scientist

St George’s Genomics Service

St George’s Hospital

Please note my working days are Wednesday – Friday

 

Website: St George's Genomics Service

St George’s, Epsom and St Helier University Hospitals and Health Group

(@stgeorges.nhs.uk emails are accredited to the DCB1596 secure email standard

and can be used to transfer confidential information between other DCB1596 email accounts including NHS.net)

 

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[Johan den Dunnen]

Dear Laura,

regarding your question, it seems the format you use to describe the variant is that of the ISCN. I suggest you contact ISCN to check whether your description follows their recommendations.

Based on HGVS nomenclature the correct description is NC_000002.12:g.[165998456_210243077del;164374088_164374089ins[165998456_210243077inv]].

First note the use of "NC_000002.12" as the reference sequence, "seq[GRCh38]chr2" can not be used in HGVS nomenclature. Second, to follow the HGVS format for allele descriptions, a set of "[ ]" was added around the description of the two different variants, [deletion;inversion].

Finally, regarding your first example, NC_000002.12:g.164374088_164374089ins[165998456_210243077inv] following HGVS nomenclature, describes only the insertion and not the deletion of the inverted segment. This would mean it describes a duplicative insertion.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op donderdag 28 augustus 2025 om 11:23:37 UTC+2 schreef Laura Cobbold: