Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781725 | SCV000919994 | uncertain significance | not specified | 2018-02-26 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.1119-18C>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. Two predict the variant creates a cryptic donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0002 in 276526 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in PKHD1 causing Polycystic Kidney and Hepatic Disease (0.0002 vs 0.0071), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1119-18C>G in individuals affected with Polycystic Kidney and Hepatic Disease and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV002067384 | SCV002338695 | likely benign | Autosomal recessive polycystic kidney disease | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003908087 | SCV004720932 | likely benign | PKHD1-related condition | 2022-05-31 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |