Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
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, |
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, |
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, |
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, |
RCV000766162 | SCV000882496 | uncertain significance | Premature ovarian insufficiency | 2018-01-10 | no assertion criteria provided | research | |
Genome Diagnostics Laboratory, |
RCV001699113 | SCV001926445 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001699113 | SCV001955861 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001699113 | SCV001969330 | pathogenic | not provided | no assertion criteria provided | clinical testing |