Table 3.

ACMG recommended categories for defining clinical significance of a CNV

CATEGORY	DEFINITION	EXAMPLE
Pathogenic	CNV is documented as clinically significant consistently and in multiple publications and/or case databases	22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome)
Uncertain (no subclassification)	Clinical significance not know at time of reporting but CNV meets the laboratory reporting criteria; expected that CNVs in this category will shift toward pathogenic or benign over time	500 kb deletion of chromosome 3 that contains 5 genes but the inheritance of the deletion is not known and there is nothing known about the 5 genes in the deleted interval
Sub-classifications:	Some evidence to increase the likelihood that the CNV is pathogenic	500 kb de novo deletion of chromosome 3 that contains 5 genes and there is a single case report in the literature that has similar breakpoints and shares a distinct phenotype
Uncertain: Likely Pathogenic
Uncertain: Likely Benign	Some evidence to increase the likelihood that the CNV is benign	500 kb deletion of chromosome 3 that does not contain any genes but is not found in any control databases
Benign	CNV is documented as benign consistently and in multiple publications and/or control databases or represents a common polymorphism (present in >1% of the population)	2q37.3 telomere polymorphism (~200 kb in size and well-documented as benign in multiple studies)

Adapted from Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, et al. Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American college of medical genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med 2011; 13(7):680-685; with permission.