ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.9319C>T (p.Arg3107Ter)

gnomAD frequency: 0.00001  dbSNP: rs786204688
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169496 SCV000220953 likely pathogenic Autosomal recessive polycystic kidney disease 2014-12-13 criteria provided, single submitter literature only
Eurofins Ntd Llc (ga) RCV000724686 SCV000231425 pathogenic not provided 2015-03-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169496 SCV000699886 pathogenic Autosomal recessive polycystic kidney disease 2016-05-13 criteria provided, single submitter clinical testing Variant summary: The PKHD1 c.9319C>T (p.Arg3107X) variant results in a premature termination codon, predicted to cause a truncated or absent PKHD1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant is located in exon 58 and PKHD1 has 67 exons, and nonsense variants downstream of this variant have been reported as pathogenic in ClinVar (i.e. p.Leu3344Ter, p.Gln3407Ter). One in silico tool predicts a damaging outcome for this variant. This variant has been reported in numerous ARPKD cases in both compound heterozygous and homozygous states, and is absent in 121354 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic.
Baylor Genetics RCV000169496 SCV001163020 pathogenic Autosomal recessive polycystic kidney disease criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002272153 SCV001427172 pathogenic Polycystic kidney disease 4 2022-06-24 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with polycystic kidney disease 4, with or without hepatic disease (MIM#263200). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity and is widely reported to show inter- and intra-familial phenotypic variability (OMIM, PMID: 12506140). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v3) <0.01 for a recessive condition (1 heterozygote, 0 homozygotes). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported multiple times as pathogenic in ClinVar. It has also been reported in multiple individuals with recessive polycystic kidney disease (PMID: 12506140, 34536170). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Invitae RCV000169496 SCV002203302 pathogenic Autosomal recessive polycystic kidney disease 2023-10-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg3107*) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with PKHD1-related conditions (PMID: 12506140, 23389334, 31010483). ClinVar contains an entry for this variant (Variation ID: 189090). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV002272153 SCV004204670 pathogenic Polycystic kidney disease 4 2023-04-27 criteria provided, single submitter clinical testing
Natera, Inc. RCV000169496 SCV002077954 pathogenic Autosomal recessive polycystic kidney disease 2017-11-30 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.