ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.2243C>T (p.Ala748Val)

gnomAD frequency: 0.00061  dbSNP: rs141622697
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV003891982 SCV000315785 likely benign PKHD1-related disorder 2023-06-30 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Eurofins Ntd Llc (ga) RCV000725680 SCV000338551 uncertain significance not provided 2018-05-29 criteria provided, single submitter clinical testing
Invitae RCV001086206 SCV000545841 likely benign Autosomal recessive polycystic kidney disease 2024-01-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000254512 SCV001362922 uncertain significance not specified 2019-05-20 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.2243C>T (p.Ala748Val) results in a non-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 0.00024 in 282530 control chromosomes, predominantly at a frequency of 0.0022 within the African subpopulation in the gnomAD database. This frequency is not higher than the expected maximum for a pathogenic variant in PKHD1 causing Polycystic Kidney and Hepatic Disease (0.0022 vs 0.0071), allowing no conclusion about variant significance. c.2243C>T has been reported in the literature in an individual affected with transitional cell carcinoma, but is unclear whether it was a germline or somatic occurrence. This report 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. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx RCV000725680 SCV001995498 uncertain significance not provided 2022-03-10 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001086206 SCV001463503 uncertain significance Autosomal recessive polycystic kidney disease 2018-05-26 no assertion criteria provided clinical testing

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