Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003619008 | SCV004540507 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2023-06-02 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 61 of the NBN protein (p.Asp61Asn). 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. 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 asparagine 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005240900 | SCV005886688 | uncertain significance | not specified | 2025-02-04 | criteria provided, single submitter | clinical testing | Variant summary: NBN c.181G>A (p.Asp61Asn) results in a conservative amino acid change located in the SMAD/FHA domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251118 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, c.181G>A has not been reported in the literature in individuals affected with Nijmegen Breakage Syndrome and no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 2910220). Based on the evidence outlined above, the variant was classified as uncertain significance. |