ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8850G>T (p.Lys2950Asn) (rs28897754)

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Total submissions: 25
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045642 SCV000073655 benign Hereditary breast and ovarian cancer syndrome 2018-01-10 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000120366 SCV000202305 likely benign not specified 2016-03-17 criteria provided, single submitter clinical testing
GeneDx RCV000120366 SCV000210674 benign not specified 2016-09-16 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 RCV000162603 SCV000213027 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Counsyl RCV000114008 SCV000220539 benign Breast-ovarian cancer, familial 2 2014-07-23 criteria provided, single submitter literature only
Vantari Genetics RCV000162603 SCV000267026 likely benign Hereditary cancer-predisposing syndrome 2016-01-06 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000114008 SCV000267822 benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000045642 SCV000267849 likely benign Hereditary breast and ovarian cancer syndrome 2016-04-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000045642 SCV000383794 likely benign Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000045642 SCV000494346 benign Hereditary breast and ovarian cancer syndrome 2014-09-26 criteria provided, single submitter clinical testing
Color RCV000162603 SCV000537411 likely benign Hereditary cancer-predisposing syndrome 2015-04-07 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120366 SCV000586985 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120366 SCV000592233 benign not specified 2015-07-22 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000120366 SCV000593733 likely benign not specified 2017-03-15 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000679194 SCV000602821 likely benign not provided 2017-11-20 criteria provided, single submitter clinical testing The BRCA2 c.8850G>T, p.Lys2950Asn variant has been identified in patients diagnosed with breast cancer (Schoumacher 2001, Kim 2005). However, multi-factorial analyses (taking into account family history, co-segregation, protein features, cancer pathology and co-occurrence) suggest that the variant is unlikely to have a deleterious effect (Easton 2007, Karchin 2008, Lindor 2012, Moghadasi 2013). The variant is listed in the dbSNP variant database (rs28897754), and classified as likely benign or benign in ClinVar (Variation ID: 52692). It is observed in the general population databases at a frequency of 0.05 percent in the Exome Variant Server (7/12999 alleles) and 0.07 percent in the Genome Aggregation Database (192/276520 alleles). The lysine is moderately conserved, and computational algorithms (Align GVGD, Mutation Taster, PolyPhen-2, SIFT) predict that the variant has an impact on the protein. However, based on the results of the multi-factorial analyses, we consider the variant to be likely benign. References: Easton D 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 81(5):873-83. Karchin R et al. Classifying Variants of Undetermined Significance in BRCA2 with protein likelihood ratios. Cancer Inform. 2008 6:203-16. Kim S et al. Prevalence of BRCA2 mutations in a hospital based series of unselected breast cancer cases. J Med Genet. 2005 42(1):e5. Lindor N et al. A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). Hum Mutat. 2012 33(1):8-21. Moghadasi S et al. Variants of uncertain significance in BRCA1 and BRCA2 assessment of in silico analysis and a proposal for communication in genetic counselling. J Med Genet. 2013 50(2):74-9. Schoumacher F et al. BRCA1/2 mutations in Swiss patients with familial or early-onset breast and ovarian cancer. Swiss Med Wkly. 2001 131(15-16):223-6.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000120366 SCV000605776 uncertain significance not specified 2016-12-21 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Lys2950Asn va riant in BRCA2 has been reported in at least 1 individual with BRCA2-associated cancer (Blay 2013). This variant has also been identified in 0.2% (21/11524) of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadi nstitute.org; dbSNP rs28897754). Computational prediction tools and conservation analysis suggest that the p.Lys2950Asn variant may impact the protein, though t his information is not predictive enough to determine pathogenicity. In summary, while the clinical significance of the p.Lys2950Asn variant is uncertain, its f requency suggests that it is more likely to be benign.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000114008 SCV000743354 benign Breast-ovarian cancer, familial 2 2014-10-09 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000114008 SCV000744551 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679194 SCV000805787 likely benign not provided 2017-03-27 criteria provided, single submitter clinical testing
Mendelics RCV000045642 SCV000838886 likely benign Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
ITMI RCV000120366 SCV000084518 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000114008 SCV000147473 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000114008 SCV000189318 benign Breast-ovarian cancer, familial 2 2011-02-25 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000120366 SCV000587973 benign not specified 2014-01-31 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000114008 SCV000733326 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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