ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.10585G>C (p.Glu3529Gln) (rs145184792)

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
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000082516 SCV000114558 benign not specified 2015-08-20 criteria provided, single submitter clinical testing
Counsyl RCV000169285 SCV000220595 likely benign Autosomal recessive polycystic kidney disease 2014-08-13 criteria provided, single submitter literature only
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224832 SCV000281593 likely benign not provided 2015-07-08 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Invitae RCV000169285 SCV000291323 benign Autosomal recessive polycystic kidney disease 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000082516 SCV000315756 likely benign not specified criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000082516 SCV000699842 benign not specified 2020-08-07 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.10585G>C (p.Glu3529Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0039 in 281654 control chromosomes, predominantly at a frequency of 0.038 within the African or African-American subpopulation in the gnomAD database (v2.1), including 21 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 5-fold of the estimated maximal expected allele frequency for a pathogenic variant in PKHD1 causing Polycystic Kidney and Hepatic Disease phenotype (0.0071), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.10585G>C has been reported in the literature in an individual affected with Polycystic Kidney and Hepatic Disease (Rossetti_2003). This report however does not provide unequivocal conclusions about association of the variant with Polycystic Kidney and Hepatic Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (4x) / likely benign (1x). Based on the evidence outlined above, the variant was classified as benign.
SIB Swiss Institute of Bioinformatics RCV000169285 SCV000803524 benign Autosomal recessive polycystic kidney disease 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Benign, for Polycystic kidney disease 4 with or without polycystic liver disease, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
Illumina Clinical Services Laboratory,Illumina RCV000169285 SCV001321744 benign Autosomal recessive polycystic kidney disease 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

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.