ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7499G>C (p.Arg2500Thr) (rs80358976)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000203647 SCV000073245 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129357 SCV000184121 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV001719711 SCV000210651 likely benign not provided 2018-07-02 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 19043619)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000045232 SCV000695070 uncertain significance not specified 2021-06-26 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.7499G>C (p.Arg2500Thr) results in a non-conservative amino acid change located in the Breast cancer type 2 susceptibility protein, helical domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251428 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.7499G>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. A recent publication involving the ENIGMA network of collaborators (Parsons_2019) assigned a classification of likely benign based on likelihood ratios (LRs) for pathogenicity estimated from clinical data of co-occurrence, family history and bioinformatic predictions; however, no evidence was provided for independent assessment. Two ClinVar submitters (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Research and Development, ARUP Laboratories RCV001642448 SCV001854928 likely benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000031682 SCV000054289 benign Breast-ovarian cancer, familial 2 2012-05-15 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031682 SCV000147107 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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