Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002470474 | SCV002767969 | likely pathogenic | Polycystic kidney disease, adult type | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with polycystic kidney disease 1 (MIM#173900). (I) 0107 - This gene is associated with autosomal dominant disease. Polycystic kidney disease 1 (MIM#173900) is predominantly caused by monoallelic variants, with rare reports of biallelic variants causing disease (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from aspartic acid to tyrosine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (1 heterozygote, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated PLAT domain (NCBI, Uniprot). (I) 0704 - Another variant comparable to the one identified in this case has limited previous evidence for pathogenicity. An inframe deletion of this residue (p.Asp3187del) has been reported as likely pathogenic. It has been observed in a family with polycystic kidney disease (PKD), and another individual with renal cysts (VCGS, LOVD, PMID: 27499327, PMID: 29338003). An alternative missense change at the same position (p.Asp3187Glu) has also been reported in an individual with PKD, however, this individual had an additional missense variant. This alternative missense variant has been classified as both likely pathogenic and indeterminate/VUS (LOVD, pkdb.mayo.edu. PMID: 22383692). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0906 - Segregation evidence for this variant is inconclusive. The variant has been segregated to this individual's affected sister, however more meioses are required for significant segregation evidence to be established. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1102 - Strong phenotype match for this individual. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |