ClinVar Miner

Submissions for variant NM_178170.3(NEK8):c.2048G>A (p.Arg683Gln)

gnomAD frequency: 0.00006  dbSNP: rs199635350
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000265888 SCV000401546 uncertain significance Nephronophthisis 9 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Fulgent Genetics, Fulgent Genetics RCV002502248 SCV002791685 uncertain significance Nephronophthisis 9; Renal-hepatic-pancreatic dysplasia 2 2022-04-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000265888 SCV003468752 uncertain significance Nephronophthisis 9 2022-07-23 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 322487). This variant has not been reported in the literature in individuals affected with NEK8-related conditions. This variant is present in population databases (rs199635350, gnomAD 0.008%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 683 of the NEK8 protein (p.Arg683Gln).
PreventionGenetics, part of Exact Sciences RCV003409507 SCV004115591 uncertain significance NEK8-related disorder 2023-06-23 criteria provided, single submitter clinical testing The NEK8 c.2048G>A variant is predicted to result in the amino acid substitution p.Arg683Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0080% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-27068587-G-A). 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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