Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000411194 | SCV000485945 | likely pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2016-03-02 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV001525393 | SCV001735472 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-12-07 | criteria provided, single submitter | clinical testing | This variant is located in the NBN protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of NBN function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Genome- |
RCV000411194 | SCV002045318 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000411194 | SCV002221912 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2024-03-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu617Lysfs*40) 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 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: 370589). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV001525393 | SCV002715141 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-03-14 | criteria provided, single submitter | clinical testing | The c.1848delA pathogenic mutation, located in coding exon 12 of the NBN gene, results from a deletion of one nucleotide at nucleotide position 1848, causing a translational frameshift with a predicted alternate stop codon (p.E617Kfs*40). 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 | RCV003470328 | SCV004191994 | likely pathogenic | Aplastic anemia | 2023-12-30 | criteria provided, single submitter | clinical testing |