Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001060946 | SCV001225667 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2021-10-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). This variant has not been reported in the literature in individuals with NBN-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys549*) in the NBN gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002402432 | SCV002704617 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-06-22 | criteria provided, single submitter | clinical testing | The p.K549* pathogenic mutation (also known as c.1645A>T), located in coding exon 11 of the NBN gene, results from an A to T substitution at nucleotide position 1645. This changes the amino acid from a lysine to a stop codon within coding exon 11. This variant was reported in 1/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). In addition to the clinical data presented in the literature, 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 | RCV003473674 | SCV004199705 | pathogenic | Aplastic anemia | 2022-12-05 | criteria provided, single submitter | clinical testing | |
| CZECANCA consortium | RCV001270950 | SCV001451754 | pathogenic | Breast and/or ovarian cancer | 2019-06-11 | no assertion criteria provided | clinical testing |