ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.7912T>A (p.Tyr2638Asn)

gnomAD frequency: 0.00002  dbSNP: rs749431123
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001876876 SCV002127856 uncertain significance Autosomal recessive polycystic kidney disease 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with asparagine at codon 2638 of the PKHD1 protein (p.Tyr2638Asn). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and asparagine. This variant is present in population databases (rs749431123, ExAC 0.006%). This missense change has been observed in individual(s) with polycystic kidney disease (PMID: 19940839). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002490052 SCV002802091 uncertain significance Polycystic kidney disease 4 2022-05-02 criteria provided, single submitter clinical testing
GeneDx RCV003107870 SCV003761948 likely pathogenic not provided 2023-01-12 criteria provided, single submitter clinical testing Observed in fetus with features consistent with ARPKD in published literature; however, this fetus was observed to have two additional PKHD1 variants, one on the same allele (in cis) and one on the opposite allele (in trans), and the effect of two of these variants on the same allele (in cis) is unknown (Denamur et al., 2010); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19940839)

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