Gene Variant (Inherited / Acquired / De Novo)
Definition
A gene variant is a permanent change in the DNA sequence that makes up a gene.
Terminology note: In the literature, the term variant is increasingly preferred over mutation, because genetic changes do not always result in disease. Seeing "variant" on your report does not necessarily mean there is a problem.
Two basic types:
| Inherited (Germline) | Acquired (Somatic) | |
|---|---|---|
| Where it comes from | From egg or sperm cells; passed on at fertilization | Arises in specific cells during a person's lifetime |
| Where it is found | In nearly every cell throughout the person's life | Only in certain cells, not throughout the body |
| Cause | Inheritance from a parent | Environmental factors such as sunlight, DNA copying errors during cell division |
| Passed on to children | Yes | No |
De novo (new) variant: A variant found in the child but present in neither parent. It may have arisen in a parent's reproductive cells or shortly after fertilization.
Why it matters: De novo variants explain genetic disorders that appear without a family history. They are usually the answer to the question "Nobody in our family has it, how can this be?" In addition, the recurrence risk is low for a subsequent pregnancy (except in the case of germline mosaicism).
Mosaicism: Different groups of cells carrying different genetic makeup:
| Type | Where | Consequence |
|---|---|---|
| Somatic mosaicism | In body cells | Effects vary depending on the severity of the variant |
| Germline mosaicism | In reproductive cells | Allows an unaffected parent to pass a genetic condition on to their child |
Why germline mosaicism is critical: A test performed on the parent's blood may come back negative, yet because the variant is present in the reproductive cells, the same disease can appear in more than one child. This explains the situation of "the test was negative, but the second child has the same disease too".
What can be passed on to a child: Only inherited (germline) variants and germline mosaicism. Somatic variants and somatic mosaicism are not passed on.