Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000792912 | SCV000932239 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2020-04-10 | criteria provided, single submitter | clinical testing | 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 sequence change replaces aspartic acid with glycine at codon 284 of the NBN protein (p.Asp284Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs772176894, ExAC 0.001%). This variant has not been reported in the literature in individuals with NBN-related disease. |
| Ambry Genetics | RCV002442616 | SCV002681555 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-24 | criteria provided, single submitter | clinical testing | The p.D284G variant (also known as c.851A>G), located in coding exon 7 of the NBN gene, results from an A to G substitution at nucleotide position 851. The aspartic acid at codon 284 is replaced by glycine, an amino acid with similar properties. This amino acid position is well 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. |