ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.212+1G>T (rs80358042)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000047717 SCV000075730 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-16 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 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 the literature in individuals and families with breast and/or ovarian cancer (PMID: 9333265, 11802209, 22970155, 26848529), as well as in an individual with prostate cancer (PMID: 22516946). This variant is also known as IVS5+1G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 54465). Different variants (c.212+1G>A, c.212+1G>C) affecting this nucleotide have been reported in individuals affected with breast and/or ovarian cancer (PMID: 19941167, 12955716, 23239986, 20215541) and has been shown to affect mRNA splicing (PMID: 20215541, 23239986), indicating that this nucleotide may be crucial for normal RNA splicing. 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.
Ambry Genetics RCV000218717 SCV000274249 pathogenic Hereditary cancer-predisposing syndrome 2015-02-24 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112019 SCV000325241 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000478644 SCV000564711 pathogenic not provided 2017-04-06 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.212+1G>T or IVS4+1G>T and consists of a G>T nucleotide substitution at the +1 position of intron 4 of the BRCA1 gene. This variant is also known as BRCA1 331+1G>T or IVS5+1G>T using alternate nomenclature. The variant destroys a canonical splice donor site and has been shown to increase the usage of an upstream cryptic splice site and result in a truncated protein (Meindl 2002, Wappenschmidt 2012). This variant has been reported in high-risk breast and/or ovarian cancer families and in at least one prostate cancer case (Shattuck-Eidens 1997, Saxena 2002, Kwong 2012, Leongamornlert 2012). We consider this variant to be pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000047717 SCV000591252 pathogenic Hereditary breast and ovarian cancer syndrome 2015-08-28 criteria provided, single submitter clinical testing
GeneKor MSA RCV000478644 SCV000693503 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Counsyl RCV000112019 SCV000785886 pathogenic Breast-ovarian cancer, familial 1 2017-12-28 criteria provided, single submitter clinical testing
Color RCV000218717 SCV000911510 pathogenic Hereditary cancer-predisposing syndrome 2017-11-02 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112019 SCV000144663 pathogenic Breast-ovarian cancer, familial 1 1999-06-21 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000112019 SCV000297588 pathogenic Breast-ovarian cancer, familial 1 2012-06-04 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000047717 SCV000587035 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.