ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2525A>G (p.Glu842Gly) (rs28897684)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077109 SCV000244322 benign Breast-ovarian cancer, familial 1 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.0000043
Ambry Genetics RCV000162977 SCV000213465 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Invitae RCV000168463 SCV000219162 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-20 criteria provided, single submitter clinical testing
Counsyl RCV000077109 SCV000487935 benign Breast-ovarian cancer, familial 1 2015-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000430143 SCV000512294 likely benign not specified 2017-08-15 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000430143 SCV000591394 likely benign not specified 2016-03-23 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000430143 SCV000600293 likely benign not specified 2017-03-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000430143 SCV000698965 likely benign not specified 2019-04-17 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2525A>G (p.Glu842Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251106 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2525A>G was originally reported in the literature in individual(s) affected with Hereditary Breast and Ovarian Cancer (Judkins_2005). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. The variant has been reported in the FLOSSIES database in two women older than age 70 years who have never had cancer, providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Studies utilizing multifactorial likelihood models to assess the clinical significance of BRCA1 variants predict this variant to be neutral/not pathogenic (Lindor_2012, Easton_2007). Six ClinVar submissions from clinical diagnostic laboratories and an expert panel (ENIGMA) (evaluation after 2014) cite the variant as likely benign (4x) and twice as benign. All submitters have utilized the same/overlapping sources of evidence utilized in this evaluation. Based on the evidence outlined above, the variant was classified as likely benign.
Color RCV000162977 SCV000911835 benign Hereditary cancer-predisposing syndrome 2016-11-21 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077109 SCV000108906 benign Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing

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