ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7007+5G>A (rs81002816)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045110 SCV000073123 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-10-28 criteria provided, single submitter clinical testing This sequence change falls in intron 13 of the BRCA2 gene. It does not directly change the encoded amino acid sequence of the BRCA2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 52239). Nucleotide substitutions within 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 may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000167485 SCV000218342 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000481869 SCV000566112 uncertain significance not provided 2018-02-14 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.7007+5G>A or IVS13+5G>A and consists of a G>A nucleotide substitution at the +5 position of intron 13 of the BRCA2 gene. Using alternate nomenclature, this variant would be defined as BRCA2 7235+5G>A. Multiple in silico models and a published computational prediction model (Mucaki 2011) predict this variant to damage or destroy the nearby natural donor site, and to possibly cause abnormal gene splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 c.7007+5G>A was not observed in large population cohorts (Lek 2016). The guanine (G) nucleotide that is altered is not conserved across species. Based on currently available information, it is unclear whether BRCA2 c.7007+5G>A is pathogenic or benign. We consider it to be a variant of uncertain significance.
Sharing Clinical Reports Project (SCRP) RCV000077393 SCV000109190 uncertain significance Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077393 SCV000146989 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735594 SCV000863732 uncertain significance Breast and/or ovarian cancer 2015-06-05 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.