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 | ||||
Uncertain | ||||
Likely neutral | ||||
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 |