Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000468237 | SCV000553040 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 393 of the NBN protein (p.Phe393Leu). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 411739). 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 leucine 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. |
Ambry Genetics | RCV000570523 | SCV000662664 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-17 | criteria provided, single submitter | clinical testing | The p.F393L variant (also known as c.1177T>C), located in coding exon 10 of the NBN gene, results from a T to C substitution at nucleotide position 1177. The phenylalanine at codon 393 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194317 | SCV001363752 | uncertain significance | not specified | 2019-01-07 | criteria provided, single submitter | clinical testing | Variant summary: NBN c.1177T>C (p.Phe393Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 30914 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1177T>C in individuals affected with Nijmegen Breakage Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Genome- |
RCV000468237 | SCV002045933 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800687 | SCV002046491 | uncertain significance | not provided | 2020-12-10 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001800687 | SCV002599692 | uncertain significance | not provided | 2023-05-04 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28539123) |
Natera, |
RCV000468237 | SCV001457041 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2020-04-14 | no assertion criteria provided | clinical testing |