ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3869G>A (p.Cys1290Tyr) (rs41293485)

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Total submissions: 25
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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) RCV000113233 SCV000245029 benign Breast-ovarian cancer, familial 2 2015-01-12 reviewed by expert panel curation Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.01423 (African), derived from 1000 genomes (2012-04-30).
Invitae RCV000167839 SCV000072307 benign Hereditary breast and ovarian cancer syndrome 2020-11-23 criteria provided, single submitter clinical testing
Counsyl RCV000113233 SCV000154085 likely benign Breast-ovarian cancer, familial 2 2014-03-18 criteria provided, single submitter literature only
Ambry Genetics RCV000128895 SCV000172755 benign Hereditary cancer-predisposing syndrome 2014-07-22 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Pathway Genomics RCV000113233 SCV000223761 benign Breast-ovarian cancer, familial 2 2014-10-30 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000113233 SCV000267762 benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120338 SCV000332977 benign not specified 2015-07-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000113233 SCV000383689 likely benign Breast-ovarian cancer, familial 2 2018-02-02 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000319921 SCV000383690 likely benign Fanconi anemia, complementation group D1 2018-02-02 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Baylor Genetics RCV000467710 SCV000541061 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000113233 SCV000575737 likely benign Breast-ovarian cancer, familial 2 2015-11-05 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000120338 SCV000593713 benign not specified 2017-06-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000120338 SCV000602782 benign not specified 2018-12-20 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514107 SCV000610415 likely benign not provided 2017-06-19 criteria provided, single submitter clinical testing
Color Health, Inc RCV000128895 SCV000683588 benign Hereditary cancer-predisposing syndrome 2015-08-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000120338 SCV001469680 benign not specified 2020-06-15 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000113233 SCV000054049 benign Breast-ovarian cancer, familial 2 2011-03-01 no assertion criteria provided clinical testing
ITMI RCV000120338 SCV000084490 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000113233 SCV000146322 benign Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120338 SCV000591880 benign not specified no assertion criteria provided clinical testing The p.Cys1290Tyr variant has been identified in 15 out of 5374 proband chromosomes (frequency 0.003) in individuals with breast cancer phenotype, however no normal population controls were included in these studies (Dufloth 2005, Borg 2010, Wagner 1999, Fackenthal 2011, Cherbal 2010). However, it is listed in dbSNP database as coming from a "clinical source" (ID#: rs41293485) with a "global minor allele frequency" of 0.003, therefore increasing the likelihood this variant is benign. The p.Cys1290 residue is not conserved in mammals and the variant amino acid tyrosine (Tyr) is present in cat, decreasing the likelihood that this variant has functional significance. In addition, in silico or computational analyses (Polyphen2, AlignGVGD, Sift) do not suggest this variant has an impact on the protein function. In the UMD database, this variant has been identified in 1 (out of 7) individuals with breast or ovarian cancers, where a second pathogenic BRCA1 mutation was also detected, further suggesting that this is a benign variant. This variant was identified in the BIC database and indicated as having no clinical significance in 47 entries. In summary, based on the above information, this variant is classified as Benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000514107 SCV000778668 likely benign not provided 2017-03-06 no assertion criteria provided clinical testing
True Health Diagnostics RCV000128895 SCV000886673 likely benign Hereditary cancer-predisposing syndrome 2018-09-06 no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120338 SCV001906030 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000514107 SCV001930523 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120338 SCV001956990 benign not specified no assertion criteria provided clinical testing

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