ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5198C>T (p.Ser1733Phe) (rs55639415)

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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000034444 SCV000883476 likely benign not provided 2018-01-02 criteria provided, single submitter clinical testing The BRCA2 c.5198C>T; p.Ser1733Phe variant (rs55639415) has been reported in the literature in individuals with breast cancer (Kraus 2017, Trujillano 2015), but is also reported in the general population with overall allele frequencies of 0.2% (9/5008 alleles) in the 1000 Genomes Project, 0.1% (14/12984 alleles) in the Exome Variant Server, and 0.05% (125/272858 alleles) in the Genome Aggregation Database. This variant is classified as benign or likely benign by multiple laboratories in ClinVar (Variation ID: 37950). Additionally, multifactorial analyses based on family history, co-segregation and co-occurrence with pathogenic variants suggests that the p.Ser1733Phe variant is unlikely to cause disease (Easton 2007). The serine at codon 1733 is moderately conserved and computational algorithms (PolyPhen2, MutationTaster, Align GVGD, Prior Probabilities) predict this variant to be tolerated. Based on the above information, this variant is considered likely benign. REFERENCES Easton DF et al. A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet. 2007 Nov;81(5):873-83. Kraus C et al. Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2. Int J Cancer. 2017 Jan 1;140(1):95-102. Trujillano D et al. Next-generation sequencing of the BRCA1 and BRCA2 genes for the genetic diagnostics of hereditary breast and/or ovarian cancer. J Mol Diagn. 2015 Mar;17(2):162-70.
Ambry Genetics RCV000163007 SCV000213495 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034444 SCV000043211 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Breast Cancer Information Core (BIC) (BRCA2) RCV000031531 SCV000146561 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000163007 SCV000683685 likely benign Hereditary cancer-predisposing syndrome 2015-04-24 criteria provided, single submitter clinical testing
Counsyl RCV000031531 SCV000154078 likely benign Breast-ovarian cancer, familial 2 2014-02-28 criteria provided, single submitter literature only
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000160228 SCV000591949 benign not specified 2013-02-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000034444 SCV000225155 uncertain significance not provided 2018-03-12 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031531 SCV000244455 benign Breast-ovarian cancer, familial 2 2015-08-10 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 = 0.000000000153
GeneDx RCV000160228 SCV000210612 benign not specified 2017-03-13 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.
Genetic Services Laboratory, University of Chicago RCV000160228 SCV000593737 likely benign not specified 2017-06-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000273833 SCV000383706 likely benign Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000044602 SCV000383707 likely benign Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000163007 SCV000747813 likely benign Hereditary cancer-predisposing syndrome 2018-01-16 criteria provided, single submitter clinical testing
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital RCV000160228 SCV000864301 likely benign not specified 2017-05-19 criteria provided, single submitter clinical testing BS1,BP4, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).
Invitae RCV000044602 SCV000072615 benign Hereditary breast and ovarian cancer syndrome 2018-01-03 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000034444 SCV000778681 likely benign not provided 2017-03-29 no assertion criteria provided clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000031531 SCV000267777 likely benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031531 SCV000054136 likely benign Breast-ovarian cancer, familial 2 2008-02-11 no assertion criteria provided clinical testing

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