Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564904 | SCV000670279 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-20 | criteria provided, single submitter | clinical testing | The c.1515delG pathogenic mutation, located in coding exon 11 of the NBN gene, results from a deletion of one nucleotide at nucleotide position 1515, causing a translational frameshift with a predicted alternate stop codon (p.E505Dfs*24). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781642 | SCV000919853 | likely pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2018-08-27 | criteria provided, single submitter | clinical testing | Variant summary: NBN c.1515delG (p.Glu505AspfsX24) 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. A truncation downstream of this position have been classified as pathogenic by our laboratory (c.2117C>G (p.Ser706X)). The variant allele was found at a frequency of 4.1e-06 in 245770 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1515delG in individuals affected with Nijmegen Breakage Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Genome- |
RCV000781642 | SCV002045327 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000781642 | SCV002234833 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu505Aspfs*24) 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). This variant is present in population databases (rs759232053, gnomAD 0.003%). 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: 484000). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV003227797 | SCV003924648 | likely pathogenic | not provided | 2023-04-26 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV003465242 | SCV004199536 | likely pathogenic | Aplastic anemia | 2024-03-26 | criteria provided, single submitter | clinical testing |