ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.49_50AC[1] (p.Arg18fs) (rs80359483)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131871 SCV000186926 pathogenic Hereditary cancer-predisposing syndrome 2017-11-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA2) RCV000113063 SCV000146071 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131871 SCV000683670 pathogenic Hereditary cancer-predisposing syndrome 2016-12-12 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113063 SCV000327129 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496563 SCV000591655 pathogenic Hereditary breast and ovarian cancer syndrome 2015-02-17 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113063 SCV000282398 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000219019 SCV000279262 pathogenic not provided 2016-01-21 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in BRCA2 is denoted c.51_52delAC at the cDNA level and p.Arg18LeufsX12 (R18LfsX12) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AGAC[AC]GCTG. The deletion causes a frameshift, which changes an Arginine to a Leucine at codon 18, and creates a premature stop codon at position 12 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.51_52delAC, previously reported as 277delAC and 279delAC, did not rescue the embryonic stem cell lethality in an in vitro functional assay, and was also observed to segregate with disease in at least one large hereditary breast/ovarian cancer family, consistent with its role as a pathogenic variant (Kuznetsov 2008, Tavtigian 1996). we consider this variant to be pathogenic.
GeneKor MSA RCV000044604 SCV000296839 pathogenic Familial cancer of breast 2016-07-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000496563 SCV000694829 pathogenic Hereditary breast and ovarian cancer syndrome 2016-01-06 criteria provided, single submitter clinical testing Variant summary: The c.51_52delAC variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein, which is a commonly known mechanism for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.8575delC). One in-silico tool predicts damaging outcome for this variant. This variant has been reported in multiple HBOC patients and not found in 118506 control chromosomes. In addition, multiple clinical laboratories/databases classified this variant as pathogenic. Taken together, this variant was classified as pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496563 SCV000587530 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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.