ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7007+4A>G (rs876661201)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000213355 SCV000279775 uncertain significance not provided 2018-05-05 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.7007+4A>G or IVS13+4A>G and consists of a A>G nucleotide substitution at the +4 position of intron 13 of the BRCA2 gene. In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant, also defined as 7235+4A>G using alternate nomenclature, has been reported in at least one individual with breast cancer (Borg 2010). BRCA2 c.7007+4A>G was not observed in large population cohorts (Lek 2016). Based on currently available information, it is unclear whether BRCA2 c.7007+4A>G is pathogenic or benign. We consider it to be a variant of uncertain significance.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258254 SCV000327564 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000474270 SCV000549491 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-20 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 been observed in an individual affected with breast cancer (PMID: 20104584). ClinVar contains an entry for this variant (Variation ID: 234756). 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 RCV000568970 SCV000668548 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000568970 SCV000905066 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-30 criteria provided, single submitter 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.