Genes are often compared to instruction manuals, as genes are a written code that make proteins, which are responsible for carrying out all of the functions of the human body. Some changes to these genes do not cause problems, like changing a capital letter to a lowercase letter: the manual can still be understood and used to make the protein. Other one-letter changes do disrupt the manual: if we change the letter N in “nail” to a “T” becoming “tail”, the instructions no longer make sense. These are called “missense” variants, and they are the most common variants seen in patients with disease-causing changes in POLR2A.
Other changes include deletions, which occur when some of the gene is missing, and premature stops, which would be like inserting a period in the middle of a sentence causing it to end early. It is possible these changes cause more intense symptoms than the missense variants, but right now there is not enough data to say with certainty.
POLR2A