ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.1032_1033del (p.Glu345fs)

dbSNP: rs1446729264
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001328217 SCV002213606 pathogenic Autosomal recessive polycystic kidney disease 2021-11-01 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 828080). This sequence change creates a premature translational stop signal (p.Glu345Serfs*12) 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 present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV001027937 SCV001190667 likely pathogenic Polycystic kidney disease 2019-05-20 no assertion criteria provided clinical testing
Sydney Genome Diagnostics, Children's Hospital Westmead RCV001328217 SCV001449402 likely pathogenic Autosomal recessive polycystic kidney disease 2018-11-23 no assertion criteria provided clinical testing This individual is heterozygous for the c.1032_1033del variant in the PKHD1 gene. This frameshifting variant is predicted to create a premature stop codon p.(Glu345Serfs*12), and may result in a null allele due to nonsense-mediated mRNA decay. This variant has been reported in the gnomAD browser (http://gnomad.broadinstitute.org) with a very low allele frequency of 0.0004% (1 out of 251,280 alleles). To our knowledge, this variant has not been previously reported in the literature or any disease specific databases. However, other truncating variants downstream of this amino acid have been reported in the literature (Bergmann et al 2005 Kid Int 67:829-848, Bergmann et al 2003 J Am Soc Nephrol 13:76-89, Obeidova et al 2015 BMC Med Genet 16:116). This variant is considered to be likely pathogenic according to the ACMG guidelines (Evidence used: PVS1, PM2).

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