ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3228_3229del (p.Gly1077fs)

dbSNP: rs80357635
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 18
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031097 SCV000282299 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000225762 SCV000076120 pathogenic Hereditary breast ovarian cancer syndrome 2021-12-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly1077Alafs*8) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357635, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 11720839, 14522380, 15477862, 16030099, 17574839, 17591843, 18819001, 18821011, 19837273, 19941167, 20104584, 22798144, 24549055, 26350514). It is commonly reported in individuals of Norwegian ancestry (PMID: 11720839, 14522380, 15477862, 16030099, 17574839, 17591843, 18819001, 18821011, 19837273, 19941167, 20104584, 22798144, 24549055, 26350514). This variant is also known as 3347delAG and c.3228delAG. ClinVar contains an entry for this variant (Variation ID: 37516). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000048107 SCV000210036 pathogenic not provided 2020-06-09 criteria provided, single submitter clinical testing Founder pathogenic variant in the Norwegian population (Ferla 2007); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 3345delAG and 3347delAG; This variant is associated with the following publications: (PMID: 10359546, 24549055, 20104584, 26350514, 27356891, 27425403, 27836010, 29061375, 29339979, 29907814, 32438681, 31336956, 19656164, 17591843, 10660329, 18821011, 14522380, 17574839, 15477862, 18819001, 22798144, 17063270, 10595257, 24312913, 15735322, 26852130, 23776375, 24131976, 19383375, 9544766, 12543786, 15519522, 18158280, 16764716, 28161869, 28637432, 28127413, 28664506, 29470806, 28724667, 29161300, 30702160, 28111427, 30720243, 32854451)
Ambry Genetics RCV000162862 SCV000213349 pathogenic Hereditary cancer-predisposing syndrome 2018-07-11 criteria provided, single submitter clinical testing The c.3228_3229delAG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 3228 to 3229, causing a translational frameshift with a predicted alternate stop codon (p.G1077Afs*8). This alteration has been detected in multiple individuals/families with hereditary breast and ovarian cancer (HBOC) syndrome (Bjørge T et al. Br. J. Cancer. 2004 Nov;91:1829-34; Kim H et al. Breast Cancer Res. Treat. 2012 Aug;134:1315-26; Alemar B et al. Cancer Genet. 2016 Sep;209:417-422; Grindedal EM et al. BMC Cancer. 2017 Jun;17:438). Due to its prevalence in Norway and Tuscany, this alteration has also been recognized as a founder mutation in these two populations (Møller P et al. Eur. J. Cancer. 2001 Dec;37:2428-34; Papi L et al. Breast Cancer Res. Treat. 2009 Oct;117:497-504). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Counsyl RCV000031097 SCV000220429 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2014-06-18 criteria provided, single submitter literature only
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000048107 SCV000296418 pathogenic not provided 2015-12-29 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031097 SCV000325582 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000473763 SCV000540936 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Department of Medical Genetics, Oslo University Hospital RCV000031097 SCV000564392 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-11-17 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162862 SCV000683092 pathogenic Hereditary cancer-predisposing syndrome 2021-08-04 criteria provided, single submitter clinical testing This variant deletes 2 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 30 individuals and families affected with breast and/or ovarian cancer (PMID: 11720839, 14522380, 14531499, 15477862, 17574839, 18819001, 18821011, 19837273, 20104584, 22798144, 24549055, 26350514, 27425403, 28637432, 28724667, 29371908, 33471991; Leiden Open Variation Database DB-ID BRCA1_000674), and it is considered a founder or recurrent mutation in the Norwegian and Italian populations (PMID: 17591843, 18821011). This variant has been identified in 1/250376 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000225762 SCV000699008 pathogenic Hereditary breast ovarian cancer syndrome 2016-11-07 criteria provided, single submitter clinical testing Variant summary: The c.3228_3229delAG (p.Gly1077Alafs) variant in BRCA1 gene is a frameshift change that is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is absent from the large control population dataset of ExAC .The variant of interest has been reported in numerous affected individuals and was shown to segregate with disease. In addition, it is cited as pathogenic by multiple reputable databases/clinical laboratories and published reports. Taking together, the variant was classified as Pathogenic.
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000048107 SCV001450357 pathogenic not provided 2017-05-30 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000048107 SCV001905568 pathogenic not provided 2021-09-15 criteria provided, single submitter clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State RCV000225762 SCV002025962 pathogenic Hereditary breast ovarian cancer syndrome 2021-11-16 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001798030 SCV002043438 pathogenic Breast and/or ovarian cancer 2020-06-17 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031097 SCV000053693 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2012-11-30 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031097 SCV000144682 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000225762 SCV000587285 pathogenic Hereditary breast 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.