Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001002146 | SCV001160001 | likely pathogenic | Polycystic kidney disease, adult type | 2018-09-25 | criteria provided, single submitter | clinical testing | The PKD1 c.10821+1G>A variant is reported in the literature in a family affected with autosomal dominant polycystic kidney disease (Hwang 2016). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant abolishes the canonical splice donor site of intron 36, which is likely to disrupt gene function. Based on available information, this variant is considered to be likely pathogenic. References: Hwang YH et al. Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol. 2016 Jun;27(6):1861-8. |
| Victorian Clinical Genetics Services, |
RCV001002146 | SCV005398193 | pathogenic | Polycystic kidney disease, adult type | 2024-10-09 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as 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) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0704 - Another canonical splice variant comparable to the one identified in this case has limited previous evidence for pathogenicity. c.10821+1G>C has been reported in two related individuals, one affected with end-stage renal disease and one affected with enlarged cystic kidneys (PMID: 19686598). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. It has been reported in multiple individuals with ADPKD (PMIDs: 37078890, 26453610, 29529603). In addition, it has been reported as likely pathogenic by a clinical laboratory (ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |