Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000637553 | SCV000759017 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-11-15 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 13 of the BRCA2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 531318). Based on a multifactorial likelihood algorithm using genetic, in silico, and/or statistical data, this variant has been determined to have a high probability of being pathogenic (PMID: 21990134). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. |
| Ambry Genetics | RCV002377382 | SCV002668140 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-17 | criteria provided, single submitter | clinical testing | The c.7007+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 12 in the BRCA2 gene. This alteration was identified in 1/3310 female patients who underwent BRCA1/2 testing in the Netherlands (Teixeira N et al. Eur J Hum Genet, 2018 06;26:848-857). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay; however, +2T>C alterations are capable of generating wild-type transcripts in some genomic contexts and should be interpreted with caution (Lin JH et al. Hum Mutat. 2019 10;40:1856-1873). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001724110 | SCV001955871 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
| Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001724110 | SCV001975586 | pathogenic | not provided | no assertion criteria provided | clinical testing |