Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670802 | SCV000795701 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2017-11-13 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000670802 | SCV004276436 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 66 of the PKHD1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 555060). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the PKHD1 protein in which other variant(s) (p.Arg3961*) have been determined to be pathogenic (PMID: 33940108; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |