ClinVar Miner

Submissions for variant NM_001199397.3(NEK1):c.1226G>A (p.Trp409Ter)

gnomAD frequency: 0.00004  dbSNP: rs985064686
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756417 SCV000884226 pathogenic not provided 2017-07-19 criteria provided, single submitter clinical testing
GeneDx RCV000756417 SCV001769578 likely pathogenic not provided 2019-04-24 criteria provided, single submitter clinical testing 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: 31589614, 27530628, 27455347, 29068549)
Revvity Omics, Revvity RCV000515987 SCV002018293 pathogenic Short-rib thoracic dysplasia 6 with or without polydactyly 2019-12-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000515987 SCV002316176 likely pathogenic Short-rib thoracic dysplasia 6 with or without polydactyly 2024-02-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp409*) in the NEK1 gene. RNA analysis indicates that this premature translational stop signal induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (no rsID available, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with clinical features of a skeletal ciliopathy (PMID: 27530628, 29068549). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 446672). Studies have shown that this premature translational stop signal results in skipping of exon 15, but is expected to preserve the integrity of the reading-frame (PMID: 27530628). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Dan Cohn Lab, University Of California Los Angeles RCV000515987 SCV000612098 pathogenic Short-rib thoracic dysplasia 6 with or without polydactyly 2017-06-01 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV000515987 SCV001479757 likely pathogenic Short-rib thoracic dysplasia 6 with or without polydactyly no assertion criteria provided research
OMIM RCV003766906 SCV004697436 pathogenic Mohr syndrome 2024-02-20 no assertion criteria provided literature only

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