ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8754G>A (p.Glu2918=) (rs80359803)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131042 SCV000185972 likely pathogenic Hereditary cancer-predisposing syndrome 2015-09-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Last nucleotide of exon,Other strong data supporting pathogenic classification,Deficient protein function in appropriate functional assay(s)
Breast Cancer Information Core (BIC) (BRCA2) RCV000077451 SCV000147451 pathogenic Breast-ovarian cancer, familial 2 2000-11-10 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077451 SCV000327958 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000523204 SCV000619052 likely pathogenic not provided 2017-07-13 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8754G>A at the DNA level. Although the variant is silent at the codinglevel, preserving a Glutamic Acid at codon 2918, it has been demonstrated to cause abnormal splicing. Located at thelast nucleotide of exon 21, it disrupts a natural splice donor site and was found to cause abnormal splicing wheninterrogated via minigene assay (Acedo 2014). This variant, also reported as BRCA2 8982G>A using alternatenomenclature, has been published in at least one individual reported to have Hereditary Breast and Ovarian Cancersyndrome (Finkelman 2012). In addition, nearby variants found to cause the same impact on splicing have beenreported in association with Hereditary Breast and Ovarian Cancer (Brandão 2011). BRCA2 c.8754G>A was notobserved in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek2016). The nucleotide which is altered, a guanine (G) at base 8754, is conserved across species. Based on currentlyavailable information, we consider BRCA2 c.8754G>A to be likely pathogenic
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496546 SCV000587968 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077451 SCV000109249 pathogenic Breast-ovarian cancer, familial 2 2010-04-15 no assertion criteria provided clinical testing

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