ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.751_754ACAG[1] (p.Asp252fs) (rs80359659)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000045245 SCV000885106 pathogenic not provided 2017-06-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162899 SCV000213386 pathogenic Hereditary cancer-predisposing syndrome 2017-07-26 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) RCV000031685 SCV000147675 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768585 SCV000219290 pathogenic Breast and/or ovarian cancer 2017-06-18 criteria provided, single submitter clinical testing
Color RCV000162899 SCV000292156 pathogenic Hereditary cancer-predisposing syndrome 2015-01-07 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031685 SCV000327681 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031685 SCV000488483 pathogenic Breast-ovarian cancer, familial 2 2016-04-15 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000167860 SCV000588071 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031685 SCV000282444 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 RCV000045245 SCV000210706 pathogenic not provided 2018-08-13 criteria provided, single submitter clinical testing This pathogenic deletion of four nucleotides in BRCA2 is denoted c.755_758delACAG at the cDNA level and p.Asp252ValfsX24 (D252VfsX24) at the protein level. The normal sequence, with the bases that are deleted in brackets, is ACAG[delACAG]TGAA. The deletion causes a frameshift, which changes an Aspartic Acid to a Valine at codon 252, and creates a premature stop codon at position 24 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.755_758delACAG, also reported as 982del4 or 983del4 using alternate nomenclature, has been published in association with breast and ovarian cancer (Tavtigian 1996, Evans 2008, Borg 2010, Kang 2015, Cao 2016, Yang 2017) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000167860 SCV000695064 pathogenic Hereditary breast and ovarian cancer syndrome 2016-07-15 criteria provided, single submitter clinical testing Variant summary: The c.755_758delACAG (p.Asp252Valfs) variant in BRCA2 gene is a frame shift predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. The variant is absent from the large control population dataset of ExAC, but has been reported in multiple affected individuals and segregated with the disease in at several families (Gayther, 1999). In addition, multiple clinical diagnostic centers classify variant as Pathogenic. Taken together, the variant was classified as Pathogenic.
Invitae RCV000167860 SCV000073258 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp252Valfs*24) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast, ovarian, and prostate cancer (PMID: 8589730, 24549055, 17636422, 23569316, 20104584, 18489799). In the literature, this variant is also known as 982del4 and 983_986del4. ClinVar contains an entry for this variant (Variation ID: 38103). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000031685 SCV000195952 pathogenic Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000045245 SCV000296717 pathogenic not provided 2015-03-05 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000167860 SCV000587567 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031685 SCV000054292 pathogenic Breast-ovarian cancer, familial 2 2012-12-21 no assertion criteria provided clinical testing

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