ClinVar Miner

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

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Total submissions: 10
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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 2018-07-24 criteria provided, single submitter clinical testing The c.81-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 2 of the BRCA1 gene. This mutation has been previously identified in multiple breast and/or ovarian cancer cohorts (Kroiss R et al. Hum Mutat. 2005 Dec;26(6):583-9; Alsop K et al. J Clin Oncol. 2012 Jul 20;30(21):2654-63). Of note, this alteration is also designated as IVS2-1G>A in published literature. In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Invitae RCV000234498 SCV000289845 pathogenic Hereditary breast and ovarian cancer syndrome 2020-06-26 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 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). Experimental studies have shown that this variant disrupts mRNA splicing and/or protein function (PMID: 30209399). 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). For these reasons, this variant has been classified as Pathogenic.
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 2020-02-25 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Truncated variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Wagner 1999, Alsop 2012, Rebbeck 2018); Not observed at a significant frequency in large population cohorts (Lek 2016); Also known as c.200-1G>A; This variant is associated with the following publications: (PMID: 25525159, 10644434, 29922827, 22711857, 29446198, 30209399, 30078507, 30720243)
Color Health, Inc RCV000131873 SCV000688672 likely pathogenic Hereditary cancer-predisposing syndrome 2019-04-09 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000478388 SCV001133649 pathogenic not provided 2018-12-24 criteria provided, single submitter clinical testing The variant disrupts a canonical splice site, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity.
Research and Development, ARUP Laboratories RCV001664264 SCV001877328 pathogenic Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2021-05-01 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000077185 SCV000108982 pathogenic Breast-ovarian cancer, familial 1 2010-08-12 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077185 SCV000144224 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000077185 SCV001241849 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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