Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000550408 | SCV000629905 | likely benign | Autosomal recessive polycystic kidney disease | 2024-01-30 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780601 | SCV000918009 | uncertain significance | not specified | 2018-08-27 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.1234-10_1234-9delinsAC alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a conflicting impact on normal splicing: One predicts the variant abolishes a 3 acceptor site. Two predict the variant weakens a 3 acceptor site. Two predict no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. Frequencies for deletions/Insertions such as this variant are not provided in the control database, gnomAD. However, the individual variants were observed with the following frequency, c.1234-10T>A: 39946/274766 (3182 homozygotes) and c.1234-9T>C: 105/274908. To our knowledge, no occurrence of c.1234-10_1234-9delinsAC in individuals affected with Polycystic Kidney and Hepatic Disease and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from another clinical diagnostic laboratory (evaluation after 2014) cites the variant as "likely benign." Based on the evidence outlined above, the variant was classified as uncertain significance. |
Gene |
RCV001764540 | SCV001998887 | uncertain significance | not provided | 2019-09-26 | criteria provided, single submitter | clinical testing | In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters 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 |