Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003504542 | SCV004293763 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2023-04-25 | criteria provided, single submitter | clinical testing | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 3, but is expected to preserve the integrity of the reading-frame (PMID: 16897190). This variant has been observed in individual(s) with polycystic kidney disease (PMID: 16897190). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change falls in intron 2 of the PKHD1 gene. It does not directly change the encoded amino acid sequence of the PKHD1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. |