ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6892G>A (p.Glu2298Lys) (rs80358914)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001088946 SCV000073098 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000218893 SCV000278351 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-18 criteria provided, single submitter clinical testing The p.E2298K variant (also known as c.6892G>A), located in coding exon 11 of the BRCA2 gene, results from a G to A substitution at nucleotide position 6892. The glutamic acid at codon 2298 is replaced by lysine, an amino acid with similar properties. This alteration was previously reported as a variant of uncertain significance in a cohort of Algerian breast/ovarian cancer families (Cherbal F et al. Dis. Markers 2012;32(6):343-53). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Counsyl RCV000083131 SCV000488459 uncertain significance Breast-ovarian cancer, familial 2 2016-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000045085 SCV000512383 likely benign not provided 2020-03-07 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 10923033, 22684231, 32046981)
Color Health, Inc RCV000218893 SCV000911664 likely benign Hereditary cancer-predisposing syndrome 2015-06-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000433666 SCV000917005 uncertain significance not specified 2020-07-03 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6892G>A (p.Glu2298Lys) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 249910 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.6892G>A has been reported in the literature in at-least one individual from a family affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Cherbal_2012). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. At-least one co-occurrence with another pathogenic variant has been reported in the BIC database (BRCA1 c.5035_5039delCTAAT, p.Leu1679_Ile1680?fs/p.Leu1679fsX2), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six 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 (likely benign, n=3; VUS, n=3). Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000045085 SCV001133879 uncertain significance not provided 2019-03-06 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083131 SCV000115205 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083131 SCV000146968 uncertain significance Breast-ovarian cancer, familial 2 2002-06-20 no assertion criteria provided clinical testing

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