ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8360G>A (p.Arg2787His) (rs80359078)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212273 SCV000210470 uncertain significance not provided 2018-02-14 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8360G>A at the cDNA level, p.Arg2787His (R2787H) at the protein level, and results in the change of an Arginine to a Histidine (CGC>CAC). Using alternate nomenclature, this variant would be defined as BRCA2 8588G>A. This variant has been observed in an individual with breast cancer whose tumor showed loss of heterozygosity, in an individual with a personal history of a Lynch syndrome associated cancer and/or polyps, but also in a woman with ovarian cancer who also carried a BRCA1 pathogenic variant (Riahi 2015, Yurgelun 2015, Riahi 2016, Eoh 2017). While the homology-directed repair activity of this variant was slightly reduced compared to the wild-type, it was comparable to other known benign and likely benign variants (Guidugli 2013, Guidugli 2018). Published multifactorial likelihood models have predicted this variant to be likely benign based on tumor pathology, clinical histories and family studies (Lindor 2012, Guidugli 2013). BRCA2 Arg2787His was not observed at a significant allele frequency in large population cohorts (Lek 2016). BRCA2 Arg2787His is located in the DSS1 contacting residues of the DNA binding domain (Yang 2002). In silico analysis, which includes protein predictors?and evolutionary conservation, support a deleterious effect. Despite some suggestion of neutrality, we consider BRCA2 Arg2787His to be a variant of uncertain significance.
Ambry Genetics RCV000214554 SCV000274666 uncertain significance Hereditary cancer-predisposing syndrome 2015-10-17 criteria provided, single submitter clinical testing
Counsyl RCV000031739 SCV000488563 likely benign Breast-ovarian cancer, familial 2 2016-04-28 criteria provided, single submitter clinical testing
Color RCV000214554 SCV000689119 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-08 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031739 SCV000054346 uncertain significance Breast-ovarian cancer, familial 2 2012-02-29 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031739 SCV000147334 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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