Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000804473 | SCV000944384 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 41 of the PKHD1 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 PKHD1 are known to be pathogenic (PMID: 19940839). This variant is not present in population databases (gnomAD no frequency). 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: 649517). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000804473 | SCV004223276 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2023-11-30 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.6809-2A>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 3 acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250822 control chromosomes (gnomAD). To our knowledge, no occurrence of c.6809-2A>T in individuals affected with Polycystic Kidney And Hepatic Disease and no experimental evidence demonstrating its impact on protein function have been reported. The following publications have been ascertained in the context of this evaluation (PMID: 35314707, 30275481). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV002290976 | SCV001163035 | likely pathogenic | Polycystic kidney disease 4 | no assertion criteria provided | clinical testing | ||
| Natera, |
RCV000804473 | SCV001459185 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2020-09-16 | no assertion criteria provided | clinical testing |