Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000547926 | SCV000634342 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2022-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 308 of the NBN protein (p.Ala308Gly). This variant is not present in population databases (gnomAD no frequency). 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: 461590). 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. 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. |
| Ambry Genetics | RCV000570689 | SCV000662747 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-22 | criteria provided, single submitter | clinical testing | The p.A308G variant (also known as c.923C>G), located in coding exon 8 of the NBN gene, results from a C to G substitution at nucleotide position 923. The alanine at codon 308 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. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Genome- |
RCV000547926 | SCV002044754 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV005398794 | SCV006058952 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency; Aplastic anemia; Acute lymphoid leukemia | 2022-06-16 | criteria provided, single submitter | clinical testing |