Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001269127 | SCV001448378 | likely pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2020-11-03 | criteria provided, single submitter | clinical testing | Variant summary: NBN c.737delG (p.Gly246ValfsX6) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251058 control chromosomes (gnomAD). To our knowledge, no occurrence of c.737delG in individuals affected with Nijmegen Breakage Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV001269127 | SCV001590058 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2021-09-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly246Valfs*6) in the NBN gene. It is expected to result in an absent or disrupted protein product. 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). |
| Genome- |
RCV001269127 | SCV002045358 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing |