ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1411G>T (p.Glu471Ter) (rs80358428)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162910 SCV000213397 pathogenic Hereditary cancer-predisposing syndrome 2018-03-07 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) RCV000112919 SCV000145868 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000162910 SCV000683423 pathogenic Hereditary cancer-predisposing syndrome 2017-02-21 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112919 SCV000326552 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112919 SCV000300428 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000043801 SCV000210269 pathogenic not provided 2017-09-21 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.1411G>T at the cDNA level and p.Glu471Ter (E471X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 1639G>T. The substitution creates a nonsense variant, changing a Glutamic Acid to a premature stop codon (GAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in at least one individual diagnosed with ovarian cancer (Susswein 2015) and it is considered pathogenic.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000112919 SCV000839925 pathogenic Breast-ovarian cancer, familial 2 2017-08-15 criteria provided, single submitter clinical testing This c.1411G>T (p.Glu471*) variant in the BRCA2 gene has been reported in three individuals with breast cancer in the Breast Cancer Information Core (BIC) database. This variant is predicted to cause loss of function of normal protein through mRNA decay or producing a truncated protein, which is a known disease mechanism for this gene. Based on the current evidence, the c.1411G>T (p.Glu471*) variant in the BRCA2 gene is classified as pathogenic.
Invitae RCV000195351 SCV000071814 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu471*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This particular truncation has been reported in the literature in an individual affected with ovarian cancer (PMID: 26681312), and two unaffected individuals with familial history of cancer (PMID: 26023681). This variant is also known as c.1638G>T and 1639G>T. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000195351 SCV000587596 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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