ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8503T>C (p.Ser2835Pro) (rs11571746)

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Total submissions: 23
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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) RCV000113950 SCV001161621 benign Breast-ovarian cancer, familial 2 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000863
Invitae RCV000167840 SCV000073553 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
Counsyl RCV000113950 SCV000154089 likely benign Breast-ovarian cancer, familial 2 2014-03-20 criteria provided, single submitter literature only
GeneDx RCV000120364 SCV000167411 benign not specified 2014-01-28 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 RCV000129146 SCV000183867 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;In silico models in agreement (benign);Intact protein function observed in appropriate functional assay(s)
Pathway Genomics RCV000113950 SCV000223756 benign Breast-ovarian cancer, familial 2 2014-10-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120364 SCV000227606 benign not specified 2015-12-16 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000113950 SCV000383785 likely benign Breast-ovarian cancer, familial 2 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000167840 SCV000494354 benign Hereditary breast and ovarian cancer syndrome 2014-09-29 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000120364 SCV000538476 likely benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.7% (77/10388) African chromosomes
Color Health, Inc RCV000129146 SCV000683973 likely benign Hereditary cancer-predisposing syndrome 2015-04-24 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283610 SCV000885095 likely benign none provided 2019-11-26 criteria provided, single submitter clinical testing
Mendelics RCV000113950 SCV001139219 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001110062 SCV001267451 likely benign Fanconi anemia, complementation group D1 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000656624 SCV001371333 likely benign not provided 2020-05-01 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001646803 SCV001852798 benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
ITMI RCV000120364 SCV000084516 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000113950 SCV000147386 benign Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000113950 SCV000592204 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing The p.Ser2835Pro variant has been identified in 7 out of 7570 proband chromosomes (frequency 0.001) in individuals with cutaneous malignant melanoma, and breast and ovarian cancer phenotypes, and identified in 1 out of 5064 control chromosomes (frequency <0.001) (Casula 2006, Caux-Moncoutier 2011, Frackenthal 2012, Johnson 2007, Palomba 2009, Tazzite 2012, Malone 2000, Karchin 2008, Schoumacher 2001). It is listed in dbSNP database as coming from a “clinical source” (ID#: rs11571746) however no frequency information was provided. The variant is identified in the EVS server as a low frequency variant increasing the likelihood this variant does not have clinical significance. The p.Ser2835 is not conserved in mammals, and computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein, and the variant amino acid Proline (Pro) residue is present in cat, dog and zebrafish, suggesting this variant may not be functionally important. In the UMD database, this variant has been identified in 2 (out of 13) individuals with breast or ovarian cancers, where a second pathogenic BRCA1 mutation was also detected, further suggesting that this is a benign variant. In addition, it is presented 34 times in the BIC database as a variant with no clinical significance. In summary based on the information presented above this variant is classified as benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000656624 SCV000778719 likely benign not provided 2018-02-05 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735612 SCV000863750 benign Breast and/or ovarian cancer 2013-04-13 no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120364 SCV001905689 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120364 SCV001952953 benign not specified no assertion criteria provided clinical testing

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