ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.1234-10_1234-9delinsAC

dbSNP: rs1554217929
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
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, LabCorp 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.
GeneDx 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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.