ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.10109dup (p.Phe3371fs)

dbSNP: rs1057517071
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000412022 SCV000486701 likely pathogenic Autosomal recessive polycystic kidney disease 2016-07-22 criteria provided, single submitter clinical testing
Invitae RCV000412022 SCV002231231 pathogenic Autosomal recessive polycystic kidney disease 2021-04-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 371184). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe3371Ilefs*3) 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).
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002470850 SCV002769165 pathogenic Polycystic kidney disease 4 2019-08-28 criteria provided, single submitter clinical testing A heterozygous duplication variant, NM_138694.3(PKHD1):c.10109dup, has been identified in exon 60 of 67 of the PKHD1 gene. This duplication is predicted to create a frameshift starting at amino acid position 3371, introducing a stop codon 3 residues downstream (NP_619639.3 (PKHD1):p.(Phe3371Ilefs*3)), resulting in loss of normal protein function through nonsense-mediated decay (NMD). This variant is predicted to result in loss of protein function through nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is absent in population databases (gnomAD, dbSNP, 1000G). The variant has been previously described as likely pathogenic (ClinVar). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.
PreventionGenetics, part of Exact Sciences RCV003401390 SCV004111420 pathogenic PKHD1-related disorder 2023-05-04 criteria provided, single submitter clinical testing The PKHD1 c.10109dupT variant is predicted to result in a frameshift and premature protein termination (p.Phe3371Ilefs*3). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant has been interpreted as pathogenic/likely pathogenic in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/371184/). Frameshift variants in PKHD1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Baylor Genetics RCV002470850 SCV004204673 likely pathogenic Polycystic kidney disease 4 2023-04-26 criteria provided, single submitter clinical testing

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