Table 1. Definition of Terms
Term Description
Genetic
variant
An alteration in the most common DNA nucleotide sequence. e
term variant can be used to describe an alteration that may be benign,
pathogenic, or of unknown significance. e term variant is increasingly
being used in place of the term mutation.
Germline
variant
A gene change in a reproductive cell (egg or sperm) that becomes
incorporated into the DNA of every cell in the body of the offspring.
A variant contained within the germline can be passed from parent to
offspring and is, therefore, hereditary.
Somatic
variant
An alteration in DNA that occurs aer conception and is not present
within the germline. Somatic variants can occur in any of the cells of the
body except the germ cells (sperm and egg ) and therefore are not passed
on to children. Somatic variants can (but do not always) cause cancer or
other diseases.
Actionable
genetic
information
e presence or absence of a genetic variant in a tumor or the germline
that can be used to inform clinical management. (Adapted from Dancey
et al. (Dancey JE, Bedard PL, Onetto N, et al.: e genetic basis for
cancer treatment decisions. Cell 148 (3): 409-20, 2012.)
Pathogenic Directly contributes to the development of disease. Additional evidence
is not expected to alter the classification of this variant. [Note: Not all
pathogenic variants are fully penetrant.]
Likely
pathogenic
Very likely to contribute to the development of disease, but scientific
evidence is currently insufficient to prove this conclusively.
Uncertain
significance
ere is not enough information at this time to support a more definitive
classification of this variant.
Likely benign Not expected to have a major effect on disease, but the scientific evidence
is currently insufficient to prove this conclusively.
Benign Does not cause disease. Additional evidence is not expected to alter
classification of this variant.
