Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001123870 | SCV001282750 | uncertain significance | Nephronophthisis 9 | 2018-01-12 | 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, |
RCV002482236 | SCV002784707 | uncertain significance | Nephronophthisis 9; Renal-hepatic-pancreatic dysplasia 2 | 2021-10-15 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001123870 | SCV003339498 | uncertain significance | Nephronophthisis 9 | 2022-03-04 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with NEK8-related conditions. This variant is present in population databases (rs368453150, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 656 of the NEK8 protein (p.Arg656Gln). ClinVar contains an entry for this variant (Variation ID: 889765). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. |
| Ambry Genetics | RCV002556683 | SCV003714300 | uncertain significance | Inborn genetic diseases | 2022-12-01 | criteria provided, single submitter | clinical testing | The c.1967G>A (p.R656Q) alteration is located in exon 14 (coding exon 14) of the NEK8 gene. This alteration results from a G to A substitution at nucleotide position 1967, causing the arginine (R) at amino acid position 656 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |