ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.6840G>A (p.Trp2280Ter)

dbSNP: rs1583295819
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001209271 SCV001380697 pathogenic Autosomal recessive polycystic kidney disease 2022-10-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 939818). 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 creates a premature translational stop signal (p.Trp2280*) 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).
3billion RCV002051922 SCV002318512 pathogenic Polycystic kidney disease 4 2022-03-22 criteria provided, single submitter clinical testing Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant.It is not observed in the gnomAD v2.1.1 dataset. This variant has been reported as pathogenic (ClinVar ID: VCV000939818, PMID:31938409, 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Neuberg Centre For Genomic Medicine, NCGM RCV002051922 SCV004176547 pathogenic Polycystic kidney disease 4 2023-02-14 criteria provided, single submitter clinical testing The stop lost c.6840G>A(p.Trp2280Ter) variant in PKHD1 gene has been reported previously in heterozygous and compound heterozygous state in patients affected with Polycystic kidney disease (Hou L, et. al., 2018). The c.6840G>A variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submissions). The nucleotide change c.6840G>A in PKHD1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. Additional functional studies are required to prove pathogenicity of the variant. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV002051922 SCV004204583 pathogenic Polycystic kidney disease 4 2023-08-15 criteria provided, single submitter clinical testing
Natera, Inc. RCV001209271 SCV002078038 pathogenic Autosomal recessive polycystic kidney disease 2020-03-11 no assertion criteria provided clinical testing

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