ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.6091del (p.Ala2031fs)

dbSNP: rs1057516804
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000412178 SCV000486249 likely pathogenic Autosomal recessive polycystic kidney disease 2016-04-22 criteria provided, single submitter clinical testing
Baylor Genetics RCV000412178 SCV001163036 likely pathogenic Autosomal recessive polycystic kidney disease criteria provided, single submitter clinical testing
Invitae RCV000412178 SCV001387999 pathogenic Autosomal recessive polycystic kidney disease 2024-01-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala2031Leufs*2) 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 clinical features of PKHD1-related conditions (PMID: 31730820, 33123899). ClinVar contains an entry for this variant (Variation ID: 370835). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000412178 SCV001519535 pathogenic Autosomal recessive polycystic kidney disease 2021-03-09 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.6091delG (p.Ala2031LeufsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251292 control chromosomes (gnomAD). c.6091delG has been reported in the literature in individuals affected with Polycystic Kidney And Hepatic Disease (Liang_2019, Qiu_2020, Wang_2021). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic an likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV000412178 SCV002078060 pathogenic Autosomal recessive polycystic kidney disease 2021-03-11 no assertion criteria provided clinical testing

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