ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7671_7672AG[1] (p.Glu2558fs) (rs80359672)

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Total submissions: 12
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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) RCV000113805 SCV000301187 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 RCV000257916 SCV000073292 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu2558Valfs*7) 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 with a personal or family history of breast and/or ovarian cancer (PMID: 27083178, 16683254, 26187060, 15131399). This variant is also known as 7901delAG in the literature. ClinVar contains an entry for this variant (Variation ID: 38113). 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 RCV000131089 SCV000186019 pathogenic Hereditary cancer-predisposing syndrome 2017-05-02 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 RCV000113805 SCV000327710 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000461632 SCV000541009 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
GeneDx RCV000485798 SCV000568486 pathogenic not provided 2016-03-15 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA2 is denoted c.7673_7674delAG at the cDNA level and p.Glu2558ValfsX7 (E2558VfsX7) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 7901delAG. The normal sequence, with the bases that are deleted in braces, is GCAG[AG]TCTT. The deletion causes a frameshift which changes a Glutamic Acid to a Valine at codon 2558, and creates a premature stop codon at position 7 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.7673_7674delAG has been observed in several individuals/families with breast and/or ovarian cancer (Lubinski 2004, van der Hout 2006, Bolognesi 2014, Ricci 2014, Kwong 2016). Based on currently available evidence, we consider this variant to be pathogenic.
Department of Medical Genetics,Oslo University Hospital RCV000113805 SCV000605639 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Color RCV000131089 SCV000689061 pathogenic Hereditary cancer-predisposing syndrome 2017-08-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000257916 SCV000695092 pathogenic Hereditary breast and ovarian cancer syndrome 2019-06-10 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.7673_7674delAG (p.Glu2558ValfsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant was absent in 251218 control chromosomes (gnomAD). c.7673_7674delAG has been reported in the literature in individuals/families affected with Hereditary Breast and Ovarian Cancer (Lubinski_2004, Ricci_2014, van der Hout_2006, Heramb_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine other submitters, including one expert panel (ENIGMA) have provided clinical-significance assessments for this variant in ClinVar after 2014, and all of them classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000485798 SCV000887920 pathogenic not provided 2018-03-13 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113805 SCV000147159 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000257916 SCV000587902 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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