Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000160237 | SCV000210637 | benign | not specified | 2014-09-08 | 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. |
| Labcorp Genetics |
RCV000196508 | SCV000253029 | likely benign | Hereditary breast ovarian cancer syndrome | 2025-01-02 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000580252 | SCV000683817 | likely benign | Hereditary cancer-predisposing syndrome | 2016-11-16 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000160237 | SCV001362776 | likely benign | not specified | 2023-12-07 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.6841+11A>G alters a non-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 allele was found at a frequency of 4.6e-05 in 281404 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in BRCA2 causing Hereditary Breast And Ovarian Cancer Syndrome (4.6e-05 vs 0.00075), allowing no conclusion about variant significance. c.6841+11A>G has been reported in the literature in at least one individual affected with breast cancer, without evidence for causality (e.g. Borg_2012). This report however, does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer Syndrome. Co-occurrence with another pathogenic variant has been reported (BRCA1 c.5154G>A, p.Trp1718X; UMD database), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |