ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.776_777GA[1] (p.Glu260fs) (rs80359677)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031701 SCV000282450 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000203632 SCV000073324 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu260Serfs*15) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant has been observed in individuals affected with breast or endometrial cancer (PMID: 8673090, 26681312, 28008555). ClinVar contains an entry for this variant (Variation ID: 38119). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131854 SCV000186909 pathogenic Hereditary cancer-predisposing syndrome 2018-03-05 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)
GeneDx RCV000045311 SCV000210708 pathogenic not provided 2018-11-13 criteria provided, single submitter clinical testing This deletion of two nucleotides is denoted BRCA2 c.778_779delGA at the cDNA level and p.Glu260SerfsX15 (E260SfsX15) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAGA[delGA]AGCT. The deletion causes a frameshift, which changes a Glutamic Acid to a Serine at codon 260, and creates a premature stop codon at position 15 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.778_779delGA, also reported as BRCA2 1006delGA using alternate nomenclature, has been reported in individuals with hereditary breast cancer, including at least one male breast cancer case (Phelan 1996, Pritzlaff 2016). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000045311 SCV000296623 pathogenic not provided 2019-08-23 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031701 SCV000327728 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000203632 SCV000695101 pathogenic Hereditary breast and ovarian cancer syndrome 2017-06-12 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.778_779delGA (p.Glu260Serfs) 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. This variant is absent in 112042 control chromosomes (ExAC). Multiple publications cite the variant in affected indivdiuals, along with multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Color RCV000131854 SCV000903407 pathogenic Hereditary cancer-predisposing syndrome 2018-02-08 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031701 SCV000054308 pathogenic Breast-ovarian cancer, familial 2 2010-12-06 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031701 SCV000145720 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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