ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3420T>C (p.Ser1140=) (rs118093942)

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Total submissions: 14
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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) RCV000113175 SCV000578021 benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/) and frequency 0.0036 (East Asian), derived from ExAC (2014-12-17).
Invitae RCV001082661 SCV000072203 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
Counsyl RCV000113175 SCV000154096 likely benign Breast-ovarian cancer, familial 2 2014-04-04 criteria provided, single submitter literature only
GeneDx RCV000123963 SCV000167355 benign not specified 2014-03-14 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.
Ambry Genetics RCV000162907 SCV000213394 likely benign Hereditary cancer-predisposing syndrome 2014-08-05 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.
Michigan Medical Genetics Laboratories,University of Michigan RCV000113175 SCV000267758 benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000113175 SCV000575745 likely benign Breast-ovarian cancer, familial 2 2015-12-08 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162907 SCV000683555 benign Hereditary cancer-predisposing syndrome 2016-05-29 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757044 SCV000885116 benign not provided 2017-09-22 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770717 SCV000902195 benign Breast and/or ovarian cancer 2017-07-05 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000757044 SCV001501466 likely benign not provided 2020-10-01 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113175 SCV000146230 benign Breast-ovarian cancer, familial 2 2010-09-18 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354013 SCV000591860 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Ser1140= variant was identified in 7 of 8452 proband chromosomes (frequency: 0.0008) from individuals or families with hereditary breast and ovarian cancer, and is classified as a benign polymorphism (Borg 2010, Dong_2015, Hu 2003, Kawahara 2004, Kim 2006, Suter 2004, Thirthagiri 2008). The variant was also identified in dbSNP (ID: rs118093942) as “With other allele”, ClinVar (as benign, reviewed by expert panel), Clinvitae (5x), COGR (as likely benign), LOVD 3.0 (4x), and UMD-LSDB (2x as "uncertain significance"). The variant was not identified in Cosmic, MutDB, BIC Database, ARUP Laboratories, or Zhejiang Colon Cancer Database. The variant was identified in control databases in 76 of 276744 chromosomes at a frequency of 0.0003 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include East Asian in 76 of 18862 chromosomes (freq: 0.004), while the variant was not observed in the African, Other, Latino, European (Non-Finnish), Ashkenazi Jewish, Finnish, and South Asian populations. The p.Ser1140= 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. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000123963 SCV001905955 benign not specified no assertion criteria provided clinical testing

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