By Diane Allingham-Hawkins, PhD, FCCMG, FACMG, Senior Director, Genetic Test Evaluation Program
Wednesday, March 26th, was the first full day of the 2014 ACMG meeting. However, on Tuesday, I attended a very interesting preconference workshop about the development of evidence-based guidelines. It was gratifying to hear that evidence is being considered more and more in clinical guidelines for genetic testing since Hayes has been a leader in providing evidence-based assessment of genetic tests since 2008.
Two major themes emerged already on day 1 of this meeting: noninvasive prenatal testing (NIPT) for common prenatal chromosome abnormalities and whole exome sequencing (WES).
NIPT is an advanced screening test for the most common numerical chromosome abnormalities (i.e., trisomy 21 [Down syndrome], trisomy 13, trisomy 18, and sex chromosome [X and Y chromosome] abnormalities). There is a lot of confusion about what these tests can and cannot tell a pregnant woman—as a screening test they are NOT diagnostic but rather give information about the chance that a pregnancy might be affected by these abnormalities. In order to be sure, an invasive diagnostic test such as chorionic villus sampling (CVS) or amniocentesis is needed. Hayes will be giving a client webinar on this topic in the first week of June, so be sure to sign up if you would like more information about these tests!
WES involves sequencing the approximately 2% of the human genome that makes up the coding regions of genes (known as exons). This technology has raced ahead of our clinical knowledge and understanding in the last several years. Consequently, there are now many questions about what this technology can (and cannot) tell us. Two major areas of concern are variants of unknown clinical significance (VUS)—essentially a genetic change that may or may not be important—and so-called “incidental findings”—genetic changes that are unrelated to the reason for testing but which may be important to the patient or their family. VUS really represent the “unknown” in genetic testing and their importance simply cannot be interpreted. This is interesting and important from a research perspective but for patients, these variants can be a source of great anxiety and uncertainty. With respect to incidental findings, someone may have WES because of a chronic kidney issue and WES may or may not identify a genetic variant that explains that issue. It is very possible, however, that a variant may be found in another gene, completely unrelated to the kidney issue, that has potential clinical significance, perhaps in a gene related to sudden cardiac death. Although this information may be important to the patient and their family, they may not have been counseled about it or consented to receiving the information. The ACMG has recommended that changes in 56 different genes should be reported to patients regardless of the indication for testing. But what if the patient is either unaware of the possibility of finding this information or chooses not to know? Should they still be told? These are the issues that are being wrestled with this week at the 2014 ACMG meeting. On Thursday, I will present our poster regarding the use of WES in rare and undiagnosed genetic conditions. We look forward to productive conversation with our genetic colleagues on these issues.
Stay tuned for more updates from the 2014 ACMG annual meeting!