Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000576388 | SCV000783720 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-12-15 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Ambry Genetics | RCV000562444 | SCV000673115 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-02-12 | criteria provided, single submitter | clinical testing | The c.7230delT pathogenic mutation, located in coding exon 13 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 7230, causing a translational frameshift with a predicted alternate stop codon (p.F2410Lfs*59). This mutation was identified in an Argentinian high-risk breast/ovarian cancer family (Solano AR et al. Oncotarget, 2017 Sep;8:60487-60495). In addition to the clinical data presented in the literature, 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. |
| Counsyl | RCV000576388 | SCV000677859 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2016-12-13 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001070667 | SCV001235931 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-10-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe2410Leufs*59) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with family history of breast/ovarian cancer (PMID: 28947987). ClinVar contains an entry for this variant (Variation ID: 485430). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001070667 | SCV004029245 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-07-10 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.7230delT (p.Phe2410LeufsX57) 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 251276 control chromosomes (gnomAD). c.7230delT has been reported in the literature in at least one individual with a family history of breast cancer (e.g., Solano_2016). The following publication was ascertained in the context of this evaluation (PMID: 28947987). Four submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic (n = 3) or likely pathogenic (n = 1). Based on the evidence outlined above, the variant was classified as pathogenic. |