ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7630G>A (p.Gly2544Ser)

dbSNP: rs587781485
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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 RCV000129445 SCV000184215 likely benign Hereditary cancer-predisposing syndrome 2020-02-25 criteria provided, single submitter clinical testing Intact protein function observed in appropriate functional assay(s)
Invitae RCV000161933 SCV000211918 uncertain significance Hereditary breast ovarian cancer syndrome 2021-08-13 criteria provided, single submitter clinical testing
Counsyl RCV000662876 SCV000785774 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2017-11-27 criteria provided, single submitter clinical testing
Eurofins NTD LLC (GA) RCV000656622 SCV000858442 uncertain significance not provided 2017-12-05 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000656622 SCV000883515 uncertain significance not provided 2017-11-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781086 SCV000918898 likely benign not specified 2021-04-30 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.7630G>A (p.Gly2544Ser) results in a non-conservative amino acid change located in the helical domain (IPR015252) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250832 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.7630G>A has been reported to co-occur with another pathogenic variant in BRCA1 (BRCA1 c.3481_3491delGAAGATACTAG, p.Glu1161PhefsX3) in a clinical sample in the literature (Schenk_2017) as well as in one internal sample, providing supporting evidence for its benign role. The literature report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer Syndrome. In Homology-directed repair (HDR) activity, the variant was found to be functional (Richardson_2021). Six other ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=5) or likely benign (n=1). Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx RCV000656622 SCV001804775 likely benign not provided 2021-04-29 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33609447, 32377563)
Genetic Services Laboratory,University of Chicago RCV000781086 SCV002065626 uncertain significance not specified 2017-11-30 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories,Mayo Clinic RCV000656622 SCV000778713 uncertain significance not provided 2017-12-07 no assertion criteria provided clinical testing

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