Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001087714 | SCV000073887 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-12-30 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588518 | SCV000695258 | uncertain significance | not provided | 2017-06-12 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA2 c.9648+10T>G variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 3/5 splice prediction tools predict an impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 2/246256 control chromosomes in gnomAD at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance, including one database indicating that the variant co-occurred with a potentially pathogenic BRCA1 variant, c.4611_4612insG (p.Gln1537_Gln1538fs). The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available. |
| Myriad Genetics, |
RCV000114141 | SCV004020270 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-03-10 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. |
| Baylor Genetics | RCV003460635 | SCV004213639 | uncertain significance | Familial cancer of breast | 2024-02-08 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000588518 | SCV005625359 | uncertain significance | not provided | 2024-05-09 | criteria provided, single submitter | clinical testing | The BRCA2 c.9648+10T>G variant has been reported in the published literature in an individual with breast cancer (PMID: 12491487 (2003)). The frequency of this variant in the general population, 0.0000071 (2/282684 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on BRCA2 mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Breast Cancer Information Core |
RCV000114141 | SCV000147685 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2010-03-10 | no assertion criteria provided | clinical testing |