ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.2280-10C>T

gnomAD frequency: 0.00004  dbSNP: rs749295454
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000593882 SCV000708434 uncertain significance not provided 2018-07-09 criteria provided, single submitter clinical testing
Invitae RCV001082366 SCV001001785 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 RCV001174910 SCV001338343 uncertain significance not specified 2020-02-29 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.2280-10C>T 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. 4/4 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 0.00021 in 251258 control chromosomes, predominantly at a frequency of 0.0012 within the Latino subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in PKHD1 causing Polycystic Kidney and Hepatic Disease allowing no conclusion about variant significance. To our knowledge, no occurrence of c.2280-10C>T in individuals affected with Polycystic Kidney and Hepatic Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001082366 SCV001463501 uncertain significance Autosomal recessive polycystic kidney disease 2017-11-16 no assertion criteria provided clinical testing

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.