ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4485-2A>G (rs80358054)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000257895 SCV000076591 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-10 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 13 of the BRCA1 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 reported in individuals affected with breast and ovarian cancer (PMID: 9333265, 11595708, 12960223, 28179634, 24249303). This variant is also known as IVS14-2A>G and 4604-2A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 55214). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV000131885 SCV000186940 likely pathogenic Hereditary cancer-predisposing syndrome 2016-03-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
GeneDx RCV000235822 SCV000293465 pathogenic not provided 2017-08-21 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4485-2A>G or IVS13-2A>G and consists of an A>G nucleotide substitution at the -2 position of intron 13 of the BRCA1 gene. Using alternate nomenclature, this variant has previously been published as BRCA1 c.4604-2A>G and BRCA1 IVS14-2A>G. This variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been reported in association with breast and ovarian cancer (Shattuck-Eidens 1997, Sekine 2001, Kwong 2015, Nakamura 2015). Based on the current evidence, we consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077574 SCV000325987 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Genologica Medica RCV000077574 SCV000577932 pathogenic Breast-ovarian cancer, familial 1 2017-01-01 criteria provided, single submitter clinical testing
Color RCV000131885 SCV000909024 likely pathogenic Hereditary cancer-predisposing syndrome 2018-10-12 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077574 SCV000109377 uncertain significance Breast-ovarian cancer, familial 1 2012-07-02 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077574 SCV000145103 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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