ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.8351A>G (p.Tyr2784Cys)

dbSNP: rs1793710520
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV002486018 SCV002777228 uncertain significance Polycystic kidney disease 4 2021-08-12 criteria provided, single submitter clinical testing
Invitae RCV001328216 SCV003206589 uncertain significance Autosomal recessive polycystic kidney disease 2022-07-06 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PKHD1 protein function. ClinVar contains an entry for this variant (Variation ID: 988201). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2784 of the PKHD1 protein (p.Tyr2784Cys).
Sydney Genome Diagnostics, Children's Hospital Westmead RCV001328216 SCV001449400 uncertain significance Autosomal recessive polycystic kidney disease 2018-07-24 no assertion criteria provided clinical testing This individual is heterozygous for the c.8351A>G variant in the PKHD1 gene. The variant has not been reported in any population databases (i.e. gnomAD, ExAC, ESP or dbSNP). To our knowledge, this variant has not been previously reported in the literature or any disease specific databases. In silico analysis of pathogenicity (through Alamut Visual v2.8.1) using PolyPhen2, SIFT and MutationTaster suggest that this variant is likely to be pathogenic. However, this analysis alone cannot be used to confirm pathogenicity. This variant is considered to be a variant of uncertain clinical significance (VOUS) according to the ACMG guidelines.

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