ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4614T>C (p.Ser1538=) (rs45520945)

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Total submissions: 18
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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) RCV000113325 SCV000578948 likely benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Invitae RCV000195330 SCV000072466 benign Hereditary breast and ovarian cancer syndrome 2020-12-01 criteria provided, single submitter clinical testing
GeneDx RCV000044453 SCV000167367 benign not specified 2014-02-05 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 RCV000163297 SCV000213825 likely benign Hereditary cancer-predisposing syndrome 2014-07-24 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.
Counsyl RCV000113325 SCV000221069 likely benign Breast-ovarian cancer, familial 2 2015-01-22 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000586489 SCV000225174 uncertain significance not provided 2014-11-13 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163297 SCV000683636 benign Hereditary cancer-predisposing syndrome 2015-11-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000044453 SCV000694787 likely benign not specified 2021-07-11 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000586489 SCV000805710 likely benign not provided 2017-06-09 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586489 SCV000889054 benign not provided 2018-06-04 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000044453 SCV001156957 likely benign not specified 2018-09-05 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000113325 SCV001429108 uncertain significance Breast-ovarian cancer, familial 2 2018-02-14 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113325 SCV000146457 uncertain significance Breast-ovarian cancer, familial 2 2007-01-18 no assertion criteria provided clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000195330 SCV000586953 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-04-14 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353663 SCV000591914 benign Malignant tumor of breast no assertion criteria provided clinical testing The p.Ser1538Ser variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. It has been reported in the literature in 3/7256 proband chromosomes of individuals with breast cancer; however, no control chromosomes were tested to establish the frequency of the variant in the general population (Borg 2010, Caux-Moncoutier 2011). It is listed in the dbSNP database as coming from a "clinical source" (ID#: rs45520945) with a global minor allele frequency (MAF) of 0.001, increasing the likelihood that this is a low frequency benign variant. The variant was also identified in the UMD (x6), BIC (x1), Exome Server and the BOCs databases. In the UMD database, this variant was identified in one individual with a second pathogenic variant in the BRCA2 gene, c.1327G>T (p.Glu443X), increasing the likelihood that the p.Ser1538Ser variant is a benign alteration. In summary, based on the above information, we cannot determine the clinical significance of this variant is classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000586489 SCV001800628 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000586489 SCV001906375 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000586489 SCV001952706 likely benign not provided no assertion criteria provided clinical testing

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