Consult about nomenclature for 3'rule

[José María García-Aznar Navajas]

To the attention of supporting team of HGVS-nomenclature,

We contact you from healthincode con consult you the consensus nomenclature of insertion according to the 3'rule.

For this instance, we detected the following variant in the PKD1 gene from NGS by using the human reference GRCh37/hg19:

NP_001009944.2:p.Asn494Profs*30

NM_001009944.2:c.1479_1480insCCTGGAGAGCTGCCAG

NC_000016.9:g.2166979_2166980insGCAGCTCTCCAGGCTG

The variant was identified in the chromosomal position chr16-2166960, however our internal variant converter was designed to be adapted with the 3'rule, so it moved the variant at the level of chromosomal coordinates. However when we consul

We are wondering if it is correct also assuming that PKD1 in placed in a negative strand. In fact the same variant is called in the databases as chr16-2166960 T>TCTGGCAGCTCTCCAGG; p.Asn494Profs*30.

We are looking forward to your response.

Sincerely,

José María García‑Aznar Navajas Head of Nephrology & Immunology (+34) 676 202 971 | (+34) 963 212 340 ext. 7319 Baños de Arteixo, 43. Business Center Marineda City, local 1A. 15008 A Coruña (Spain) healthincode.com

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[Johan den Dunnen]

Dear José Maria,

a correct description of the variant you mention is NC_000016.10:g.2116963_2116978dup

NM_001009944.2:c.1464_1479dup p.(Asn494ProfsTer30). The 3'rule has to be applied related to the reference sequence used. 

For a gene on the negative strand, it might indeed mean that the alignment shifts. Please also note that, following HGVS nomenclature, 

the variant must be described as an insertion (see the prioritization rules). In addition, since it are predicted consequences, the 

variant at protein level needs to be given as p.(Asn494ProfsTer30) (i.e. in parenthesis).

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op vrijdag 6 juni 2025 om 11:01:27 UTC+2 schreef José María García-Aznar Navajas: