ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5074+2T>C (rs80358089)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031212 SCV001161641 pathogenic Breast-ovarian cancer, familial 1 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 0.999563
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031212 SCV000326134 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000465250 SCV000549302 pathogenic Hereditary breast and ovarian cancer syndrome 2020-01-21 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 16 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 observed in several individuals affected with breast cancer and/or ovarian cancer (PMID: 25556971, 27914478, 28717669, 29339979, 29446198). This variant is also known as IVS17+2T>C in the literature. ClinVar contains an entry for this variant (Variation ID: 37631). 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.
Department of Medical Genetics, Oslo University Hospital RCV000031212 SCV000564328 likely pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563483 SCV000660953 pathogenic Hereditary cancer-predisposing syndrome 2018-12-26 criteria provided, single submitter clinical testing The c.5074+2T>C intronic pathogenic mutation results from a T to C substitution two nucleotides after coding exon 15 in the BRCA1 gene. This alteration has been previously reported in multiple patients undergoing genetic testing based on personal and/or family history concerning for hereditary breast and ovarian cancer (HBOC) syndrome (Trujillano D et al. J Mol Diagn. 2015 Mar;17:162-70; Lourenco J et al. Genet Mol Biol. Sao Paulo. 2004;27(4):500-504). 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.
Color Health, Inc RCV000563483 SCV000683248 pathogenic Hereditary cancer-predisposing syndrome 2020-05-07 criteria provided, single submitter clinical testing
Mendelics RCV000465250 SCV000839219 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000031212 SCV001140493 pathogenic Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001659878 SCV001877440 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) RCV000031212 SCV000053812 pathogenic Breast-ovarian cancer, familial 1 2009-03-06 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031212 SCV000145290 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000465250 SCV000587453 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353976 SCV000591567 pathogenic Malignant tumor of breast no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000031212 SCV001237537 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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