ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5363G>A (p.Gly1788Asp) (rs80357069)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077620 SCV001161715 uncertain significance Breast-ovarian cancer, familial 1 2019-03-25 reviewed by expert panel curation To our knowledge this variant has only been seen alone once, in a male control in gnomAD (South Asian population). Clinical evidence in Goldgar et al 2004 (PMID: 15290653) is not applicable unless this variant is observed in cis with c.5359T>A (Variation ID 55548). We recommend that if c.5363G>A is detected in an individual, presence of c.5359T>A should be assessed. Functional assay data analysis of the c.5363G>A variant suggests that it is unlikely to alter protein function alone, but that it does alter function when in combination with BRCA1 c.5359T>A (PMID: 30765603; 30209399). For more information see the haplotype entry BRCA1 c.[5359T>A;5363G>A] (Variant ID 624568).
Cancer Variant Interpretation Group UK, Institute of Cancer Research, London RCV001542250 SCV001760922 uncertain significance Hereditary breast and ovarian cancer syndrome 2021-07-09 criteria provided, single submitter reference population Data included in classification: Prevalence in cases vs controls is increased (PS4_sup) Absent from non-cancer females in gnomAD (PM2_mod). Critical residue within BRCT domain (PM1_mod). REVEL 0.862 (PP3_sup). Parsons et al, 2019 combined LR: 0.0457 (BP6_str). Data not included in classification: Conflicting functional data: Lee et al 2010 PMID: 20516115 = VUS Gaboriau et al 2015 PMID: 25748678 = 30-50% HR activity (VUS) Woods et al 2016 PMID: 28781887 = VUS Findlay et al 2018 PMID: 30209399 = FUNC (G1788V & G1788C both LOF), Bouwman et al 2020 PMID: 32546644 = Cisplatin NEUTRAL, Olaparib DEL, DR-GFP DEL G1788C and G1788V (class 5) also reported at this position (PM5 not applied due to conflicting functional data and PM1 already having been applied)
Research and Development, ARUP Laboratories RCV001664104 SCV001878770 uncertain significance 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) RCV000077620 SCV000109423 pathogenic Breast-ovarian cancer, familial 1 2008-04-07 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077620 SCV000145481 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496269 SCV000587503 uncertain significance not specified 2014-01-31 no assertion criteria provided research
Brotman Baty Institute,University of Washington RCV000077620 SCV001242677 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.