Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000434390 | SCV000527316 | likely benign | not specified | 2017-12-01 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589603 | SCV000695150 | uncertain significance | not provided | 2016-05-16 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA2 c.8487+4T>C variant involves the alteration of a non-conserved intronic nucleotide with 5/5 splice prediction tools calculating no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP), nor has it been, to our knowledge, reported in affected individuals via publications. A reputable database cites the variant as "uncertain significance." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available. |
| Labcorp Genetics |
RCV001300602 | SCV001489748 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-09-09 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 19 of the BRCA2 gene. It does not directly change the encoded amino acid sequence of the BRCA2 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 52604). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002444502 | SCV002680827 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-16 | criteria provided, single submitter | clinical testing | The c.8487+4T>C intronic variant results from a T to C substitution 4 nucleotides after coding exon 18 in the BRCA2 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Breast Cancer Information Core |
RCV000113947 | SCV000147380 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | no assertion criteria provided | clinical testing |