Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001004199 | SCV001163039 | pathogenic | Autosomal recessive polycystic kidney disease | criteria provided, single submitter | clinical testing | ||
| Invitae | RCV001004199 | SCV001202247 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-09-13 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 35 of the PKHD1 gene. It does not directly change the encoded amino acid sequence of the PKHD1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of autosomal recessive polycystic kidney disease (PMID: 15805161, 27225849, 33123899). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 813379). 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 create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
| Victorian Clinical Genetics Services, |
RCV002471012 | SCV002766967 | pathogenic | Polycystic kidney disease 4 | 2022-09-02 | 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 4, with or without hepatic disease (MIM#263200. (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Significant intra-familial variability has been reported (GeneReviews). (I) 0212 - Non-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) 0705 - No comparable splice site variants have previous evidence for pathogenicity. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported as compound heterozygotes in at least three individuals with ARPKD and classified as likely pathogenic or pathogenic by diagnostic laboratories in ClinVar (PMID: 15805161, 27225849, 33123899). (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 |
| Baylor Genetics | RCV002471012 | SCV004204701 | pathogenic | Polycystic kidney disease 4 | 2023-03-22 | criteria provided, single submitter | clinical testing |