Description MLPA deletion

[Claudio Paolicelli]

Dear HGVS support,

I have a question about the description in case of  deletion. I found with MLPA analysis a deletion of Exon 23 to Exon 32 of USH2A gene. In the section "Reccomandation-DNA-deletion" i have read the exampe about deletion of Exon 30 to Exon 32 of DMD gene, i downloaded the MLPA datasheet Holland P034-035 and i have considered cDNA positions. 

The ligation site position of Exon 29 probes is 3990-3991. Why do i have to consider position 3996 as reported in the deletion section? Same problem for the other positions to use for the descripion of the deletion. Indeed, in the section "Uncertain" is reported "the description of the variant detected uses the basic format (last-normal-position_first-altered-position)_(last-altered-position_first-normal-position). For MLPA, the probe position is the ligation site, i.e. the first nucleotide of the probe 3' of the ligation site. For MLPA probes containing two ligation sites, the probe position is the central nucleotide between the two ligation sites (when two nucleotides form the center the 3' rule applies and the 3'nucleotide is selected).

Example: for exon 24 of the DMD gene (NM_004006.2), the ligation site is ..ATGGCCTGCCCTTGGGGATTCAGA.., i.e. the T nucleotides c.3233 and c.3234. Since the DMD gene is on the - strand, nucleotide NM_004006.2:c.3233 is therefore used as the probe position in variant descriptions." 

About deletion Exon30-36 of DMD gene, is correct the description         

c.(3990_4193)_(5080_5289)del?

Thanks for your help

Dr. Claudio Paolicelli

Biologist, Specialist in medical Genetics

University Tor Vergata, Rome.

[Johan den Dunnen]

Dear Claudio,

regarding your question, "About deletion Exon30-36 of DMD gene, is correct the description c.(3990_4193)_(5080_5289)del?". Yes following HGVS nomenclature, this description is correct.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op dinsdag 1 april 2025 om 12:44:58 UTC+2 schreef Claudio Paolicelli: