Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000591197 | SCV000709595 | uncertain significance | not provided | 2017-06-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001088505 | SCV001014131 | likely benign | Autosomal recessive polycystic kidney disease | 2024-01-16 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174777 | SCV001338106 | uncertain significance | not specified | 2020-01-23 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.7734-6C>A 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. 2/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 7.1e-05 in 282508 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in PKHD1 causing Polycystic Kidney and Hepatic Disease (7.1e-05 vs 0.0071), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.7734-6C>A in individuals affected with Polycystic Kidney and Hepatic Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (1x) and likely benign (1x). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Gene |
RCV000591197 | SCV002001154 | uncertain significance | not provided | 2020-06-29 | criteria provided, single submitter | clinical testing | In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge |