ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.8345G>C (p.Gly2782Ala) (rs147222255)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000082581 SCV000114623 likely benign not specified 2015-10-05 criteria provided, single submitter clinical testing
Invitae RCV000659055 SCV000557652 likely benign not provided 2019-03-05 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000082581 SCV000592904 uncertain significance not specified 2016-09-27 criteria provided, single submitter clinical testing
Institute of Human Genetics,Klinikum rechts der Isar RCV000473573 SCV000680338 likely pathogenic Autosomal recessive polycystic kidney disease 2017-12-07 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000659055 SCV000780862 uncertain significance not provided 2017-12-01 criteria provided, single submitter clinical testing
Counsyl RCV000473573 SCV000799007 uncertain significance Autosomal recessive polycystic kidney disease 2018-04-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000082581 SCV000918005 likely benign not specified 2019-06-06 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.8345G>C (p.Gly2782Ala) results in a non-conservative amino acid change located in the second G8 domain (IPR019316) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0027 in 251184 control chromosomes, including 3 homozygotes (gnomAD, exomes dataset). The variant was predominantly found within the Non-Finnish European subpopulation at a frequency of 0.005 that is somewhat lower than the maximum expected allele frequency for a pathogenic variant in PKHD1 causing Polycystic Kidney and Hepatic Disease (0.0071). The variant has also been reported in in the literature, where it was identified in 2/200 healthy control chromosomes (Sharp 2005, Bergmann 2005), and was listed as a polymorphism (benign) based on the criteria proposed by the authors. These reports do 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. Six other submitters have provided clinical-significance assessments for this variant in ClinVar after 2014 (without evidence for independent evaluation), and classified the variant with conflicting assessments: likely pathogenic (1x), VUS (3x), likely benign (2x). Based on the evidence outlined above, the variant was classified as likely 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.