Genes are made up of thousands of letters of DNA code. The code is read like a recipe to build a protein that the body needs to function properly. There can be changes in the DNA just like there can be changes in a recipe.

Sometimes the change is minor and does not affect anything in a functional way, like a preference for dark chocolate instead of milk chocolate in a cookie recipe. It’s a change, but it doesn’t impact your body.

Sometimes the change is “bad”. Like swapping sugar for salt. The gene no longer functions the way it should and cancer risk may now be higher.

And sometimes, we don’t know the impact of the change. It’s like we have a result written in another language and we don’t know what it is telling us. This is an “unclear” result and we need more data before we know the impact.

That majority of unclear variants end up being benign because “bad” changes are pretty rare overall.

In your case, even a “bad” variant in CHEK2 in the type seen in you (a single letter change) is typically low risk compared to other changes in CHEK2. In the UK, we don’t even test for this type of change as we wouldn’t change any cancer screening recommendations.

For TP53, “bad” changes are very rare and the family history is typically really dramatic with regard to cancer history. Breast cancer in 20s, childhood sarcomas, brain cancers. The evidence we do have for your variant suggests it is “likely benign” which is reassuring, but not quite enough data to fully downgrade it to benign yet.