ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7521A>G (p.Pro2507=) (rs759383358)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163178 SCV000213699 benign Hereditary cancer-predisposing syndrome 2016-03-01 criteria provided, single submitter clinical testing
Color RCV000163178 SCV000683882 benign Hereditary cancer-predisposing syndrome 2016-04-19 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000444567 SCV000592119 likely benign not specified 2013-02-18 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000191161 SCV000244472 benign Breast-ovarian cancer, familial 2 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 = 0.0000989
GeneDx RCV000444567 SCV000512387 benign not specified 2015-03-18 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 RCV000444567 SCV000918949 uncertain significance not specified 2018-08-24 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.7521A>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.2e-05 in 277144 control chromosomes, exclusively found within the East Asian subpopulation at a frequency of 0.00048 in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.7521A>G has been reported in the literature in a Chinese individual affected with Hereditary Breast and Ovarian Cancer (Zhong 2016). However, based on multifactorial likelihood analysis the variant was classified as Class 1, i.e. not pathogenic or of little clinical significance (Whiley 2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the vat as benign (4x) / likely benign (2x) / VUS (1x). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Invitae RCV000200714 SCV000253037 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-18 criteria provided, single submitter clinical testing
Laboratory of Molecular Diagnosis of Cancer,West China Hospital, Sichuan University RCV000240774 SCV000265957 uncertain significance Neoplasm of the breast 2015-11-01 criteria provided, single submitter research
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759659 SCV000889130 likely benign not provided 2017-12-08 criteria provided, single submitter clinical testing

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