Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001023075 | SCV001184895 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-11 | criteria provided, single submitter | clinical testing | The p.Y16C variant (also known as c.47A>G), located in coding exon 2 of the NBN gene, results from an A to G substitution at nucleotide position 47. The tyrosine at codon 16 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800935 | SCV002046398 | uncertain significance | not provided | 2020-11-10 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003507351 | SCV004272517 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2023-09-25 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with NBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 825184). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 16 of the NBN protein (p.Tyr16Cys). |