ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1138del (p.Ser380fs) (rs80359264)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
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) RCV000077251 SCV000300387 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000043744 SCV000071757 pathogenic Hereditary breast and ovarian cancer syndrome 2018-06-20 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide in exon 10 of the BRCA2 mRNA (c.1138delA), causing a frameshift at codon 380. This creates a premature translational stop signal (p.Ser380Valfs*19) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in the literature in an individual with personal and/or family history of breast and/or ovarian cancer (PMID: 18779604). This variant is also known as 1366delA in the literature. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000132193 SCV000187273 pathogenic Hereditary cancer-predisposing syndrome 2016-07-15 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)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077251 SCV000326502 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000505982 SCV000600465 pathogenic not provided 2016-11-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000043744 SCV000694511 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-01 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1138delA (p.Ser380Valfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay (NMD), which are commonly known mechanisms for disease. If this variant escapes NMD, it is expected to truncate functional domains such as helical, oligonucleotide/oligosaccharide-binding and Tower domains. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Gln486X, p.Leu557X, p.Gln619X, etc). This variant is absent in approximately 120780 control chromosomes from ExAC but has been reported in multiple patients with HBOC in literature and clinical databases. Multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic.
GeneDx RCV000505982 SCV000779130 pathogenic not provided 2017-10-18 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.1138delA at the cDNA level and p.Ser380ValfsX19 (S380VfsX19) at the protein level. The normal sequence, with the base that is deleted in brackets, is TGGA[delA]GTGA. The deletion causes a frameshift which changes a Serine to a Valine at codon 380, and creates a premature stop codon at position 19 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.1138delA, also reported as 1366delA using alternate nomenclature, has been reported in individuals undergoing BRCA1/2 testing for a personal and/or family history of breast and ovarian cancer (Alemar 2016, Fernandes 2016). We consider this variant to be pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077251 SCV000109048 pathogenic Breast-ovarian cancer, familial 2 2010-07-12 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077251 SCV000145820 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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.