ClinVar Miner

Submissions for variant NM_178170.3(NEK8):c.1795C>T (p.Arg599Ter)

gnomAD frequency: 0.00007  dbSNP: rs375661404
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001699113 SCV002038937 pathogenic not provided 2022-09-19 criteria provided, single submitter clinical testing Loss of NEK8 expression was reported in fibroblasts from affected fetuses with this homozygous variant (Frank et al., 2013); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26697755, 30924587, 31980526, 31589614, 23418306, 26862157)
Fulgent Genetics, Fulgent Genetics RCV002483083 SCV002784663 pathogenic Nephronophthisis 9; Renal-hepatic-pancreatic dysplasia 2 2022-04-06 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000055629 SCV003920972 likely pathogenic Renal-hepatic-pancreatic dysplasia 2 2023-03-23 criteria provided, single submitter clinical testing This variant was observed in heterozygosity with variant c.618G>A
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV000055629 SCV004808066 likely pathogenic Renal-hepatic-pancreatic dysplasia 2 2024-03-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000055629 SCV005185988 pathogenic Renal-hepatic-pancreatic dysplasia 2 2024-05-02 criteria provided, single submitter clinical testing Variant summary: NEK8 c.1795C>T (p.Arg599X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 6.8e-05 in 251416 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in NEK8 causing Renal-Hepatic Dysplasia 2. c.1795C>T has been reported in the literature in multiple homozygous individuals affected with Renal-Hepatic Dysplasia 2 (e.g., Frank_2013). These data indicate that the variant is very likely to be associated with disease. One publication reports experimental evidence evaluating an impact on protein function; studies on patient fibroblasts demonstrated a loss of NEK8 expression. The following publication has been ascertained in the context of this evaluation (PMID: 23418306). ClinVar contains an entry for this variant (Variation ID: 65408). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000055629 SCV000083854 pathogenic Renal-hepatic-pancreatic dysplasia 2 2013-06-01 no assertion criteria provided literature only
Reproductive Development, Murdoch Childrens Research Institute RCV000766162 SCV000882496 uncertain significance Premature ovarian insufficiency 2018-01-10 no assertion criteria provided research
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001699113 SCV001926445 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001699113 SCV001955861 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001699113 SCV001969330 pathogenic not provided no assertion criteria provided clinical testing

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