Question about Alu insertion nomenclature

[Asier Iturrate]

Dear HGVS team,

I have a question about the nomenclature of an Alu insertion I have detected. The structure of the insertion is as follows: AluY + A[22] + 17 bp target site duplication (TSD).

My concern is that when I search for my AluY sequence in the human genome (GRCh38) using BLAT, I get a total of 5 exact matches.

Assuming I want to use the following nomenclature:

NC_000001.11: g.X_Yins [AluY_coordinates ; A[22] ; Z_X]

Where X, Y and Z are the genomic coordinates of my insertion and TSD, respectively

Which of the 5 matches should I use? Does the one I select in my variant nomenclature have any additional meaning apart from sequence identity? (For example, if I select the match on chromosome 4, does that mean that the Alu in my mutation was previously located on chromosome 4?)

Thank you so much in advance, 

Best wishes, 

Asier Iturrate

[Johan den Dunnen]

Dear Asier,

an interesting case. I do not think this case, i.e. multiple exact copies of an inserted sequence can be found in the genome, is mentioned in the HGVS nomenclature. One could argue that in this case you should also apply the 3' rule ("for all descriptions, the most 3' position possible of the reference sequence is arbitrarily assigned to have been changed"), i.e. you should use the most 3' copy of the exact Alu-match in the genome. Note that for chromosome, following ISCN recommendations, the order for 5' to 3' is chromosome X, Y, 1, 2, 3, ..., 21, 22.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op donderdag 3 juli 2025 om 08:33:39 UTC+2 schreef asierit...@gmail.com: