ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3575T>G (p.Phe1192Cys) (rs80358606)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755858 SCV000883474 uncertain significance not provided 2017-07-10 criteria provided, single submitter clinical testing The BRCA2 c.3575T>G; p.Phe1192Cys variant (rs80358606) is reported in the ClinVar database as uncertain or likely benign (Variation ID: 51490), and observed in general population databases with an allele frequency of 0.13 percent (45/34404 alleles) in Latinos in the Genome Aggregation Database. The phenylalanine at codon 1192 is weakly conserved across species and computational algorithms (Align GVGD, SIFT, MutationTaster, Prior Probabilities) predict this variant to be tolerated. However, with the limited information regarding p.Phe1192Cys, its clinical significance is uncertain at this time. REFERENCES Link to ClinVar database for p.Phe1192Cys: https://www.ncbi.nlm.nih.gov/clinvar/variation/51490/
Ambry Genetics RCV000130786 SCV000185679 likely benign Hereditary cancer-predisposing syndrome 2017-09-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: No disease association in appropriately sized case-control study(ies)
Breast Cancer Information Core (BIC) (BRCA2) RCV000077308 SCV000146261 uncertain significance Breast-ovarian cancer, familial 2 2001-10-29 no assertion criteria provided clinical testing
Color RCV000130786 SCV000903289 likely benign Hereditary cancer-predisposing syndrome 2017-04-26 criteria provided, single submitter clinical testing
Counsyl RCV000077308 SCV000489626 uncertain significance Breast-ovarian cancer, familial 2 2016-11-02 criteria provided, single submitter clinical testing
GeneDx RCV000254642 SCV000210593 likely benign not specified 2017-10-09 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.
Integrated Genetics/Laboratory Corporation of America RCV000254642 SCV000694706 likely benign not specified 2018-08-03 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3575T>G (p.Phe1192Cys) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 1.73 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00075), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. c.3575T>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Lee_2008). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000044226 SCV000072239 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000254642 SCV000296713 uncertain significance not specified 2017-04-25 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077308 SCV000109105 likely benign Breast-ovarian cancer, familial 2 2012-07-09 no assertion criteria provided clinical testing

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