Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001204081 | SCV001375270 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2023-04-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 935481). This variant has not been reported in the literature in individuals affected with NBN-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln581*) in the NBN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). |
| Gene |
RCV001204081 | SCV002011819 | likely pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2019-03-05 | criteria provided, single submitter | clinical testing | This variant causes in a premature truncation of the NBN protein product, designated as p.Q581* or p.Gln581Ter. This substitution is predicted to result in a non-functional NBN protein, either through protein truncation or nonsense-mediated mRNA decay. It is considered a non-tolerated amino acid change based on “in silico” prediction algorithms (disease causing), and it has been reported in the gnomAD database at a frequency of 0.000004. Based on these findings and the limited literature regarding this substitution we consider it as a “likely pathogenic variant”. |
| Genome- |
RCV001204081 | SCV002045322 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002411748 | SCV002715190 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-02 | criteria provided, single submitter | clinical testing | The p.Q581* pathogenic mutation (also known as c.1741C>T), located in coding exon 11 of the NBN gene, results from a C to T substitution at nucleotide position 1741. This changes the amino acid from a glutamine to a stop codon within coding exon 11. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Baylor Genetics | RCV003473744 | SCV004199634 | likely pathogenic | Aplastic anemia | 2023-06-15 | criteria provided, single submitter | clinical testing |