ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.603-2A>G

gnomAD frequency: 0.00001  dbSNP: rs757521428
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411920 SCV000485407 likely pathogenic Autosomal recessive polycystic kidney disease 2015-12-11 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000411920 SCV000894386 likely pathogenic Autosomal recessive polycystic kidney disease 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000411920 SCV001575161 likely pathogenic Autosomal recessive polycystic kidney disease 2023-11-20 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 8 of the PKHD1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant is present in population databases (rs757521428, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 370164). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV003475940 SCV004202220 likely pathogenic Polycystic kidney disease 4 2023-11-07 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV003475940 SCV005382414 likely pathogenic Polycystic kidney disease 4 2023-05-20 criteria provided, single submitter clinical testing The splice acceptor c.603-2A>G variant in the PKHD1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency (0.001%) in the gnomAD Exomes. This sequence change affects an acceptor splice site in intron 8 of the PKHD1 gene. This variant is predicted to cause a loss of normal protein function through protein truncation. Loss of function variants has been previously reported to be disease causing (Michel-Calemard et al., 2009). For these reasons, this variant has been classified as Likely Pathogenic.
Natera, Inc. RCV000411920 SCV002083399 likely pathogenic Autosomal recessive polycystic kidney disease 2019-02-04 no assertion criteria provided clinical testing

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