ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.81-1G>A (rs80358018)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131873 SCV000186928 pathogenic Hereditary cancer-predisposing syndrome 2015-06-29 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) (BRCA1) RCV000077185 SCV000144224 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Color RCV000131873 SCV000688672 likely pathogenic Hereditary cancer-predisposing syndrome 2018-08-29 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077185 SCV000326431 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000478388 SCV000567462 pathogenic not provided 2018-09-06 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.81-1G>A or IVS2-1G>A and consists of a G>A nucleotide substitution at the -1 position of intron 2 of the BRCA1 gene. Using alternate nomenclature, this variant has previously been published as BRCA1 200-1G>A. This variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to 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 hereditary breast and ovarian cancer syndrome (Wagner 1999, Alsop 2012, Rebbeck 2018). Based on the current evidence, we consider this variant to be pathogenic.
Invitae RCV000234498 SCV000289845 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-15 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the BRCA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs80358018, ExAC 0.002%). This variant has been observed in an individuals affected with breast cancer (PMID: 10644434) and ovarian cancer (PMID: 22711857). This variant is also known as 200-1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 91668). 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.
Sharing Clinical Reports Project (SCRP) RCV000077185 SCV000108982 pathogenic Breast-ovarian cancer, familial 1 2010-08-12 no assertion criteria provided clinical testing

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