Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000796428 | SCV000935941 | uncertain significance | Short-rib thoracic dysplasia 6 with or without polydactyly | 2024-11-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 355 of the NEK1 protein (p.Arg355Gly). This variant is present in population databases (rs35763578, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with NEK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 642879). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt NEK1 protein function with a negative predictive value of 95%. 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. |
| Illumina Laboratory Services, |
RCV000796428 | SCV001306882 | likely benign | Short-rib thoracic dysplasia 6 with or without polydactyly | 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
| ARUP Laboratories, |
RCV003117586 | SCV003799567 | uncertain significance | not provided | 2022-03-15 | criteria provided, single submitter | clinical testing | The NEK1 c.1063A>G; p.Arg355Gly variant (rs35763578), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 642879). This variant is found in the general population with an overall allele frequency of 0.0066% (13/196588 alleles) in the Genome Aggregation Database. The arginine at codon 355 is moderately conserved, and computational analyses predict that this variant is neutral (REVEL: 0.082). Due to limited information, the clinical significance of this variant is uncertain at this time. |
| Gene |
RCV003117586 | SCV003923940 | uncertain significance | not provided | 2022-11-07 | 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; This variant is associated with the following publications: (PMID: 27527004) |