Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003405147 | SCV004121973 | uncertain significance | not specified | 2023-10-20 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.893_895delATA (p.Asp298_Ile299delinsVal) results in an in-frame deletion-insertion that is predicted to delete two amino acids (DI) from the protein and changes it with a different amino acid (V). Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250714 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.893_895delATA has been reported in the literature in at-least one individual from a Autosomal recessive polycystic kidney disease cohort study, however, authors classified the variant as VUS (example: Burgmaier_2021). This report does not provide unequivocal conclusions about association of the variant with Polycystic Kidney And Hepatic Disease. The following publication has been ascertained in the context of this evaluation (PMID: 33940108). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |