Submissions for variant NM_000297.4(PKD2):c.181C>T (p.Gln61Ter)

gnomAD frequency: 0.00001  dbSNP: rs1355372474

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV000788302	SCV000927359	likely pathogenic	not provided	2017-07-27	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292152	SCV001480729	pathogenic	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD2 p.Gln61X variant was not identified in the literature nor was it identified in the following databases: dbSNP, ClinVar, COGR, LOVD 3.0, or PKD1-LOVD. The variant was identified in the ADPKD Mutation Database (as definitely pathogenic) and in control databases in 1 of 80646 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017); it was observed in the East Asian population in 1 of 2940 chromosomes (freq: 0.0003). The c.181C>T variant leads to a premature stop codon at position 61 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the PKD2 gene are an established mechanism of disease in autosomal dominant polycystic kidney disease and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.