ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.631+1G>A (rs81002897)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131851 SCV000186906 pathogenic Hereditary cancer-predisposing syndrome 2015-04-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other acmg-defined mutation (i.e. initiation codon or gross deletion),Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Breast Cancer Information Core (BIC) (BRCA2) RCV000113913 SCV000147335 pathogenic Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113913 SCV000327383 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000113913 SCV000677667 likely pathogenic Breast-ovarian cancer, familial 2 2017-02-27 criteria provided, single submitter clinical testing
Invitae RCV000044895 SCV000072908 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-11 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the BRCA2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in two individuals affected with Fanconi anemia (FA) (PMID: 16825431, 15004464). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant has also been reported in individuals affected with breast cancer (PMID: 27393621). This sequence change is also known as IVS7+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 9348). Experimental studies have shown that this sequence change results in the out-of-frame skipping of exon 7. This is expected to create a premature translational stop signal (p.Val211Serfs*19), resulting in an absent or disrupted protein product (PMID: 15004464). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000009942 SCV000030163 pathogenic Fanconi anemia, complementation group D1 2007-01-01 no assertion criteria provided literature only

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