ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9257-16T>C (rs11571818)

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Total submissions: 21
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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) RCV000114078 SCV000245297 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 0.01055 (European), derived from 1000 genomes (2012-04-30).
Invitae RCV000045764 SCV000073777 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Counsyl RCV000114078 SCV000154101 benign Breast-ovarian cancer, familial 2 2014-04-10 criteria provided, single submitter literature only
Michigan Medical Genetics Laboratories,University of Michigan RCV000114078 SCV000196024 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000152886 SCV000202306 benign not specified 2015-10-13 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000152886 SCV000301782 benign not specified criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000045764 SCV000494375 benign Hereditary breast and ovarian cancer syndrome 2014-02-03 criteria provided, single submitter clinical testing
Color Health, Inc RCV000446929 SCV000537380 benign Hereditary cancer-predisposing syndrome 2014-12-09 criteria provided, single submitter clinical testing
Baylor Genetics RCV000468147 SCV000541044 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000114078 SCV000575764 benign Breast-ovarian cancer, familial 2 2016-02-22 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000152886 SCV000586991 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283530 SCV000602757 benign none provided 2020-08-07 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000114078 SCV000743362 benign Breast-ovarian cancer, familial 2 2014-10-09 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000114078 SCV000744560 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000114078 SCV000147587 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000114078 SCV000189322 benign Breast-ovarian cancer, familial 2 2011-03-15 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000152886 SCV000592269 benign not specified no assertion criteria provided clinical testing The BRCA2 c.9257-16T>C variant was identified in 121 of 53524 proband chromosomes (frequency: 0.002) from individuals or families with Breast and Ovarian cancer, and was present in 4 of 530 control chromosomes (frequency: 0.08) from healthy individuals (Caputo 2011, Borg 2010, Hadijisavvas 2003, Cvok 2008, Diez 2003). The variant was identified in dbSNP (ID: rs11571818) with “other” allele, with a minor allele frequency of 0.0044(1000 Genomes Project); in NHLBI Exome Sequencing Project (Exome Variant Server) in 67 of 8600 European and 10 of 4406 African Americans; in Exome Aggregation Consortium (ExAC) database in 574(3 homozygote) of 56204 of Europeans(non-Finnish), in 15 of 9522 Africans, in 25 of 10298 Latinos, in 116 (4 homozygote) of 15288 South Asians , in 77 (2 homozygote) of 6222 Europeans (Finnish) and 5 of 820 other populations, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. The variant was also found in LOVD, the ClinVar database (classified as a benign variant by the Sharing Clinical Reports Project, derived from Myriad reports, classified as benign by Invitae, as benign by Counsyl, as benign by GeneDX, as benign by Emory Genetics, as Likely benign by CHEO and as uncertain significance by BIC). It was also identified in GeneInsight through the Canadian Open Genetics Repository (http://opengenetics.ca/) (1X, classified as “likely benign” by a clinical laboratory), the BIC database (12X with no clinical importance), and UMD (73X as a neutral variant). In UMD the variant was identified with a co-occurring pathogenic BRCA1 and BRCA2 variants (BRCA1:c.5116G>A (p.Gly1706Arg), c.4391delC (p.Pro1464LeufsX2), c.81_134delp.Cys27X); BRCA2:c.6275_6276delTT (p.Leu2092ProfsX7), c.4889C>G (p.Ser1630X), increasing the likelihood that the c.9257-16T>C variant does not have clinical significance. The c.9257-16T>C variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In addition splicing studies (Bonnet 2008, Claes 2003) showed that the c.9257-16T>C do not result in aberrant splicing. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000114078 SCV000733336 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001573242 SCV001798803 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000152886 SCV001905684 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000152886 SCV001954160 benign not specified no assertion criteria provided clinical testing

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