Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000484053 | SCV000565311 | uncertain significance | not provided | 2016-06-20 | criteria provided, single submitter | clinical testing | This variant is denoted NBN c.1654G>C at the cDNA level, p.Glu552Gln (E552Q) at the protein level, and results in the change of a Glutamic Acid to a Glutamine (GAA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NBN Glu552Gln was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamic Acid and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. NBN Glu552Gln occurs at a position that is not conserved and is not located in a known functional domain (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether NBN Glu552Gln is pathogenic or benign. We consider it to be a variant of uncertain significance. |
| Labcorp Genetics |
RCV000554168 | SCV000634242 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 552 of the NBN protein (p.Glu552Gln). 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: 418376). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The glutamine 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 | RCV001012604 | SCV001173076 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-22 | criteria provided, single submitter | clinical testing | The p.E552Q variant (also known as c.1654G>C), located in coding exon 11 of the NBN gene, results from a G to C substitution at nucleotide position 1654. The glutamic acid at codon 552 is replaced by glutamine, an amino acid with highly 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. |
| Genome- |
RCV000554168 | SCV002044578 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003470528 | SCV004199520 | uncertain significance | Aplastic anemia | 2023-10-17 | criteria provided, single submitter | clinical testing |