ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6803G>A (p.Arg2268Lys) (rs80358906)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001086840 SCV000073068 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131556 SCV000186558 benign Hereditary cancer-predisposing syndrome 2016-08-22 criteria provided, single submitter clinical testing Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
Michigan Medical Genetics Laboratories,University of Michigan RCV000077385 SCV000195999 uncertain significance Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
GeneDx RCV000045055 SCV000210636 likely benign not specified 2017-07-27 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000587611 SCV000225158 uncertain significance not provided 2015-03-12 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045055 SCV000592075 uncertain significance not specified 2012-03-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000045055 SCV000600719 uncertain significance not specified 2017-04-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000045055 SCV000694997 likely benign not specified 2019-12-06 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6803G>A (p.Arg2268Lys) results in a conservative amino acid change located in the outside of any known functional domain or repeat of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 250550 control chromosomes, predominantly at a frequency of 0.00051 within the African or African-American subpopulation in the gnomAD database. The variant has also been observed in a database of unaffected cancer free individuals of African American ancestry at age greater than 70 (FLOSSIES database). c.6803G>A has been reported in the literature in sequencing studies of individuals affected with Breast and/or Ovarian Cancers (example, Dutil_2012, Fackenthal_2012, Haiman_2013, Balmaa_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported ( BRCA1 c.815_824dupAGCCATGTGG , p.Thr276fsX14) (BIC database) including one publication that reported a co-occurrence with an unspecified deleterious mutation (Dutil_2012) 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 ranging from benign/likely benign (n=4) to VUS (n=2) reporting overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as likely benign.
Color RCV000131556 SCV000902982 likely benign Hereditary cancer-predisposing syndrome 2016-04-28 criteria provided, single submitter clinical testing
Mendelics RCV000077385 SCV001139157 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077385 SCV000109182 benign Breast-ovarian cancer, familial 2 2010-12-28 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077385 SCV000146938 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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