ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5199C>T (p.Ser1733=) (rs28897734)

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Total submissions: 31
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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) RCV000113396 SCV000577985 benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.0109 (Finnish), derived from ExAC (2014-12-17).
Invitae RCV000044603 SCV000072616 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
Counsyl RCV000113396 SCV000154097 likely benign Breast-ovarian cancer, familial 2 2014-04-04 criteria provided, single submitter literature only
GeneDx RCV000152876 SCV000167371 benign not specified 2013-10-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Michigan Medical Genetics Laboratories,University of Michigan RCV000113396 SCV000195989 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000152876 SCV000202288 benign not specified 2016-01-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162368 SCV000212676 likely benign Hereditary cancer-predisposing syndrome 2014-05-28 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768598 SCV000219348 benign Breast and/or ovarian cancer 2016-11-11 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000113396 SCV000383708 likely benign Breast-ovarian cancer, familial 2 2018-03-20 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.
Illumina Clinical Services Laboratory,Illumina RCV000277308 SCV000383709 likely benign Fanconi anemia, complementation group D1 2018-03-20 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000044603 SCV000494329 benign Hereditary breast and ovarian cancer syndrome 2014-01-27 criteria provided, single submitter clinical testing
Baylor Genetics RCV000475668 SCV000541048 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488323 SCV000574953 likely benign not provided 2021-06-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000113396 SCV000575739 likely benign Breast-ovarian cancer, familial 2 2015-10-19 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000152876 SCV000586958 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000152876 SCV000588098 benign not specified 2017-04-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282970 SCV000602774 benign none provided 2020-07-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000152876 SCV000605772 benign not specified 2016-05-23 criteria provided, single submitter clinical testing p.Ser1733Ser in exon 11 of BRCA2: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 1.09% (72/6606) of Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs28897734).
Color Health, Inc RCV000162368 SCV000683686 benign Hereditary cancer-predisposing syndrome 2015-04-06 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000113396 SCV000743304 benign Breast-ovarian cancer, familial 2 2014-10-10 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000113396 SCV000744464 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000152876 SCV000805718 benign not specified 2017-02-02 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113396 SCV000146562 benign Breast-ovarian cancer, familial 2 2000-06-12 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000113396 SCV000189308 benign Breast-ovarian cancer, familial 2 2011-03-14 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000152876 SCV000591950 benign not specified no assertion criteria provided clinical testing The BRCA2 p.Ser1733Ser variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site; in addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified in 76 of 12892 proband chromosomes (frequency: 0.006) from individuals or families with breast or ovarian cancer, or pancreatic carcinoma/melanoma-prone families (Balabas 2010, Bartsch 2009, Borg 2010, Schroeder 2010, Slater 2010, Stegel 2011, van der Hout 2006, Wagner 1999, Weber 2006, Yang 2009). The variant was also present in 5 of 310 control chromosomes (frequency: 0.016) from healthy individuals (Cvok 2008, Stegel 2011). The variant was identified in dbSNP (ID: rs28897734) with a minor allele frequency of 0.0016 (1000 Genomes Project), NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) database, Clinvitae database, Fanconi Anemia Mutation Database (LOVD), COSMIC, the ClinVar database (classified as “benign” by six submitters and “likely benign” by two submitters), GeneInsight COGR database (submitted by three clinical laboratories, with classifications of benign, presumed benign, and unclassified), the BIC database (11X with no clinical importance), and the BRCA Share (UMD) database (95X with a neutral classification). In the BRCA Share database, 15 samples were listed with co-occurring pathogenic BRCA1 or BRCA2 variants, increasing the likelihood that the p.Ser1733Ser variant is not clinically significant. The variant was identified at polymorphic allelic frequencies in two HAPMAP populations listed in the variant’s dbSNP record: HAPMAP-TSI (Toscans in Italy) and HAPMAP-MEX (Mexican ancestry in Los Angeles). The variant is also found at a polymorphic frequency (72/6606 alleles, frequency 0.0109) in a population of European (Finnish) individuals identified in the Exome Aggregation Consortium (ExAC) database; one of these individuals was homozygous for the variant, and two individuals from a cohort of European (Non-Finnish) were also homozygotes, increasing the likelihood of this being a benign variant. In addition, Myriad classifies this variant as a polymorphism (personal communication). 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 RCV000113396 SCV000733262 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000488323 SCV000778682 benign not provided 2017-05-15 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162368 SCV000787935 likely benign Hereditary cancer-predisposing syndrome 2017-09-29 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000152876 SCV001799242 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000152876 SCV001906249 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000152876 SCV001954614 benign not specified no assertion criteria provided clinical testing

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