ClinVar Miner

Submissions for variant NM_178170.3(NEK8):c.583G>A (p.Glu195Lys)

gnomAD frequency: 0.00011  dbSNP: rs752331372
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000548256 SCV000650632 uncertain significance Nephronophthisis 9 2022-08-12 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 471780). This variant has not been reported in the literature in individuals affected with NEK8-related conditions. This variant is present in population databases (rs752331372, gnomAD 0.06%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 195 of the NEK8 protein (p.Glu195Lys).
GeneDx RCV002221555 SCV002499005 uncertain significance not provided 2022-11-21 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002483469 SCV002786165 uncertain significance Nephronophthisis 9; Renal-hepatic-pancreatic dysplasia 2 2022-04-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003387880 SCV004100295 uncertain significance not specified 2023-09-29 criteria provided, single submitter clinical testing Variant summary: NEK8 c.583G>A (p.Glu195Lys) results in a conservative amino acid change located in the Protein kinase domain (IPR000719) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.8e-05 in 250840 control chromosomes (gnomAD). To our knowledge, no occurrence of c.583G>A in individuals affected with Renal-Hepatic Dysplasia 2 and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences RCV004754468 SCV005356767 uncertain significance NEK8-related disorder 2024-08-24 no assertion criteria provided clinical testing The NEK8 c.583G>A variant is predicted to result in the amino acid substitution p.Glu195Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.051% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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