Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586448 | SCV000697953 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2016-10-06 | criteria provided, single submitter | clinical testing | Variant summary: The c.175C>T (p.Gln59*) variant in NBN gene is a nonsense change that results in the loss of the 696 amino acids of NBN (~90%). This change is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is absent from control dataset of ExAC and has not, to our knowledge, been reported in affected individuals via published reports or cited by a reputable database/clinical laboratory. Biallelic truncating mutations in NBN are associated with Nijmegen breakage syndrome whereas heterozygous carriers of a truncated variant have an increased cancer risk. Taking together, the variant was classified as Likely Pathogenic. |
| Labcorp Genetics |
RCV000688264 | SCV000815869 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln59*) 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: 496163). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV001013002 | SCV001173532 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-16 | criteria provided, single submitter | clinical testing | The p.Q59* pathogenic mutation (also known as c.175C>T), located in coding exon 3 of the NBN gene, results from a C to T substitution at nucleotide position 175. This changes the amino acid from a glutamine to a stop codon within coding exon 3. 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. |
| Genome- |
RCV000688264 | SCV002045377 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV003133388 | SCV003808658 | likely pathogenic | not provided | 2021-12-31 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003471944 | SCV004199620 | likely pathogenic | Aplastic anemia | 2023-07-27 | criteria provided, single submitter | clinical testing |