Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000519783 | SCV000617248 | likely pathogenic | not provided | 2017-10-03 | criteria provided, single submitter | clinical testing | The c.2020-1_2020delGA variant in the PDK2 gene has been reported previously, using alternate nomenclature c.2020-2_-1delAG, in an individual with autosomal dominant polycystic kidney disease (Hoefele et al., 2011). This splice site variant destroys the canonical splice acceptor site in intron 9, which is predicted to cause abnormal gene splicing. The c.2020-1_2020delGA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.2020-1_2020delGA as a likely pathogenic variant. |
| Cavalleri Lab, |
RCV001095628 | SCV001251266 | pathogenic | Polycystic kidney disease 2 | 2020-02-05 | criteria provided, single submitter | research | PVS1, PM2, PP4 |
| Invitae | RCV001387315 | SCV001587916 | pathogenic | Autosomal dominant polycystic kidney disease | 2022-01-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 449307). This variant is also known as c.2020-1_2020del, c.2020-2_-1delAG (IVS9-2_-1delAG). Disruption of this splice site has been observed in individuals with polycystic kidney disease (PMID: 21115670, 27499327). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 10 of the PKD2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PKD2 are known to be pathogenic (PMID: 17582161, 22863349). |
| Fulgent Genetics, |
RCV001095628 | SCV002810406 | pathogenic | Polycystic kidney disease 2 | 2022-01-04 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001292171 | SCV001480796 | pathogenic | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD2 c.2020-1_2020delGA variant was identified in the literature however the frequency of this variant in an affected population was not provided (Yu 2011, Hoefele 2011). The variant was also identified in the ADPKD Mutation Database (classified as definitely pathogenic). The variant was not identified in dbSNP, ClinVar, Clinvitae, COGR, or LOVD 3.0 databases nor in the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The variant has been found in one Chinese ADPKD family (described using the nomenclature c.2020-2_1, but resulting in the same splice variant) and in a German family with at least one ADPKD affected family member (Yu, 2011, Hoefele, 2011). The c.2020-1_2020del variant results in a deletion of the critical -1 canonical splice site nucleotide, is located in the 5’ splice site and 4 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a difference in splicing. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. |