ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1302_1305AAGA[2] (p.Lys437fs) (rs80359277)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 19
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131062 SCV000185992 pathogenic Hereditary cancer-predisposing syndrome 2018-02-23 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),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Breast Cancer Information Core (BIC) (BRCA2) RCV000031318 SCV000145851 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131062 SCV000688704 pathogenic Hereditary cancer-predisposing syndrome 2017-05-03 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031318 SCV000326537 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031318 SCV000221095 pathogenic Breast-ovarian cancer, familial 2 2015-01-28 criteria provided, single submitter literature only
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031318 SCV000744407 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000203644 SCV000591735 pathogenic Hereditary breast and ovarian cancer syndrome 2013-03-13 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000031318 SCV000733227 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000043779 SCV000224771 pathogenic not provided 2014-12-23 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031318 SCV000282355 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 RCV000043779 SCV000210713 pathogenic not provided 2018-11-28 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA2 is denoted c.1310_1313delAAGA at the cDNA level and p.Lys437IlefsX22 (K437IfsX22) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAGA[delAAGA]TTTTC. The deletion causes a frameshift, which changes a Lysine to an Isoleucine at codon 437, and creates a premature stop codon at position 22 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.1310_1313delAAGA, previously reported as BRCA2 1310del4, 1537del4, and 1538del4 using alternate nomenclature, has been reported in the heterozygous state in association with hereditary breast and ovarian cancer and in the homozygous state in a child with Fanconi Anemia (Gayther 1997, Zhang 2011, Caputo 2012, Kang 2015, Malric 2015, Laarabi 2017). Furthermore, this variant was shown in a functional study to decrease BRCA2 mRNA expression levels in fibroblasts from BRCA2 carriers (Jonsdottir 2009). We consider this variant to be pathogenic.
GeneKor MSA RCV000043779 SCV000693556 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Genologica Medica RCV000031318 SCV000577946 pathogenic Breast-ovarian cancer, familial 2 2017-01-01 criteria provided, single submitter clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785565 SCV000924137 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Integrated Genetics/Laboratory Corporation of America RCV000203644 SCV000694532 pathogenic Hereditary breast and ovarian cancer syndrome 2017-05-01 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1310_1313delAAGA (p.Lys437Ilefs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.c.1456C>T (p.Gln486X) and c.1654delT (p.Ser552fs)). This variant was found in 1/120430 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). This variant has been reported in multiple HBOC patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000203644 SCV000071792 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys437Ilefs*22) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80359277, ExAC 0.01%). This variant has been reported in the literature in numerous individuals and families affected with breast and/or ovarian cancer (PMID: 22144684, 18465347, 12955716, 8988179, 20683152, 25863477). This variant is also known as 1538del4 and 1529del4 in the literature. ClinVar contains an entry for this variant (Variation ID: 37737). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000043779 SCV000296609 pathogenic not provided 2015-09-29 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000203644 SCV000587590 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031318 SCV000053923 pathogenic Breast-ovarian cancer, familial 2 2012-10-04 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.