Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Cavalleri Lab, |
RCV001095617 | SCV001251254 | likely pathogenic | Polycystic kidney disease 2 | 2020-02-05 | criteria provided, single submitter | research | PM2, PP2, PP3, PP4, PP5 |
Fulgent Genetics, |
RCV001095617 | SCV002812938 | pathogenic | Polycystic kidney disease 2 | 2022-02-19 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002554878 | SCV003598714 | likely pathogenic | Inborn genetic diseases | 2021-12-28 | criteria provided, single submitter | clinical testing | The c.974G>A (p.R325Q) alteration is located in exon 4 (coding exon 4) of the PKD2 gene. This alteration results from a G to A substitution at nucleotide position 974, causing the arginine (R) at amino acid position 325 to be replaced by a glutamine (Q). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been identified in several families with autosomal dominant polycystic kidney disease (Rossetti, 2007; Cornec-Le Gall, 2017; Kim, 2019; Mantovani, 2020). Based on the available evidence, this alteration is classified as likely pathogenic. |
Gene |
RCV003151832 | SCV003840618 | likely pathogenic | not provided | 2023-03-07 | criteria provided, single submitter | clinical testing | Published functional studies suggest p.(R325Q) leads to loss of ciliary current and shift of voltage-dependent channel opening (Vien et al., 2020); Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 20950398, 31740684, 22008521, 36763973, 32457805, 33454723, 28356211, 17582161, 32332171) |
Prevention |
RCV003405299 | SCV004107639 | pathogenic | PKD2-related condition | 2023-09-27 | criteria provided, single submitter | clinical testing | The PKD2 c.974G>A variant is predicted to result in the amino acid substitution p.Arg325Gln. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant has been reported to segregate with autosomal dominant polycystic kidney disease (ADPKD) in a family and was classified as a “highly likely pathogenic” variant (Rossetti et al. 2007. PubMed ID: 17582161). Later, it was repeatedly reported in other presumably unrelated individuals with polycystic kidney disease (Bataille et al. 2011. PubMed ID: 22008521; Kim et al. 2019. PubMed ID: 31740684, supplementary tables; Vien et al. 2020. PubMed ID: 32332171; Benson et al. 2021. PubMed ID: 33454723, Suppl. Table 3). The Vien et al. study suggested that variants located within the TOP domain of polycystin-2 (encoded by PKD2), including this variant, result in failure to open the channels at normal voltages although the channels can be normally assembled. Of note, we have found this variant in the heterozygous state in presumably unrelated patients tested for polycystic kidney disease at PreventionGenetics. Taken together, this variant is interpreted as pathogenic. |