Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000480332 | SCV000570007 | uncertain significance | not provided | 2016-04-21 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.8954-13T>C or IVS22-13T>C and consists of a T>C nucleotide substitution at the -13 position of intron 22 of the BRCA2 gene. Using alternate nomenclature, this variant would be defined as BRCA2 9182-13T>C. Although one model is uninformative, at least one in silico model predicts this variant to damage the nearby natural acceptor site and to possibly cause abnormal gene splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 c.8954-13T>C was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The thymine (T) nucleotide that is altered is not conserved across species. Based on currently available information, it is unclear whether BRCA2 c.8954-13T>C is pathogenic or benign. We consider it to be a variant of uncertain significance. |
| Color Diagnostics, |
RCV000775938 | SCV000910436 | likely benign | Hereditary cancer-predisposing syndrome | 2020-07-22 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001584197 | SCV001821425 | likely benign | not specified | 2024-12-18 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.8954-13T>C alters a conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250472 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8954-13T>C has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome, without strong evidence for causality (John_2024). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 38538877). ClinVar contains an entry for this variant (Variation ID: 420962). Based on the evidence outlined above, the variant was classified as likely benign. |
| Labcorp Genetics |
RCV002056788 | SCV002380662 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-10-02 | criteria provided, single submitter | clinical testing |