title: ENIGMA--evidence-based network for the interpretation of germline mutant alleles: an international initiative to evaluate risk and clinical significance associated with sequence variation in BRCA1 and BRCA2 genes.
abstract: As genetic testing for predisposition to human diseases has become an increasingly common practice in medicine, the need for clear interpretation of the test results is apparent. However, for many disease genes, including the breast cancer susceptibility genes BRCA1 and BRCA2, a significant fraction of tests results in the detection of a genetic variant for which disease association is not known. The finding of an "unclassified" variant (UV)/variant of uncertain significance (VUS) complicates genetic test reporting and counseling. As these variants are individually rare, a large collaboration of researchers and clinicians will facilitate studies to assess their association with cancer predisposition. It was with this in mind that the ENIGMA consortium (www.enigmaconsortium.org) was initiated in 2009. The membership is both international and interdisciplinary, and currently includes more than 100 research scientists and clinicians from 19 countries. Within ENIGMA, there are presently six working groups focused on the following topics: analysis, clinical, database, functional, tumor histopathology, and mRNA splicing. ENIGMA provides a mechanism to pool resources, exchange methods and data, and coordinately develop and apply algorithms for classification of variants in BRCA1 and BRCA2. It is envisaged that the research and clinical application of models developed by ENIGMA will be relevant to the interpretation of sequence variants in other disease genes.
authors: Queensland Institute of Medical Research, Brisbane, Australia.
authors: Amanda B
authors: AB
authors: Spurdle
authors: Sue
authors: S
authors: Healey
authors: Andrew
authors: A
authors: Devereau
authors: Frans B L
authors: FB
authors: Hogervorst
authors: Alvaro N A
authors: AN
authors: Monteiro
authors: Katherine L
authors: KL
authors: Nathanson
authors: Paolo
authors: P
authors: Radice
authors: Dominique
authors: D
authors: Stoppa-Lyonnet
authors: Sean
authors: S
authors: Tavtigian
authors: Barbara
authors: B
authors: Wappenschmidt
authors: Fergus J
authors: FJ
authors: Couch
authors: David E
authors: DE
authors: Goldgar
mesh_terms: D000465:Algorithms; D000483:Alleles; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics; D003627:Data Interpretation, Statistical; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods* / Q000592:standards; D014644:Genetic Variation; D005854:Germ Cells; D018095:Germ-Line Mutation; D006801:Humans; D009934:Organization and Administration; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics; D017410:Practice Guidelines as Topic; D012326:RNA Splicing; D012307:Risk Factors