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Table 1 Examples of recommendations for genetic variant classification

From: Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come?

Working group affiliation National affiliations of participating researchers Dates of approval, publishing, or update Proposed number of variant classifications Proposed classification categories
American College of Medical Genetics [26] United States 2007; revisions published April 2008 6 (1) Previously reported and is causative of the disorder
(2) Not previously reported but expected to cause the disorder
(3) Not previously reported and may or may not cause the disorder
(4) Not previously reported but probably does not cause the disorder
(5) Previously reported and known to be neutral
(6) Not expected to cause the disorder but reported to be associated with a clinical presentationa
European Society of Human Genetics [35] France, Czech Republic, Belgium, Switzerland, the Netherlands, Germany, Slovenia, Italy, United Kingdom, Ireland Published online August 2013; published in the European Journal of Human Genetics 2014 5 Normal (physiological finding, normal variation) findings
Non-specific findings without clinical relevance
Incidental findings with possible clinical relevance
Findings of uncertain significance
Pathognomonic (disease-specific, pathological) findings
International Agency for Research on Cancer [18] (World Health Organization) Australia, Canada, France, Italy, the Netherlands, United Kingdom, United States November 2008 5 Pathogenic
Likely pathogenic
Likely neutral
UK Clinical Molecular Genetics Society and Association of Clinical Cytogenetics [25] United Kingdom Ratified 11 January, 2008; update approved and published September 2013 5 (1) Clearly not pathogenic
(2) Unlikely to be pathogenic
(3) Unknown significance (VUS)
(4) Likely to be pathogenic
(5) Clearly pathogenic
Dutch Society of Clinical Genetic Laboratory Specialists [25] The Netherlands Ratified 22 October, 2007; update approved and published September 2013
  1. aCategories have been summarized for brevity. VUS, variants of uncertain significance.