Secondary Findings: What Should Be Reported?

Secondary Findings: What Should Be Reported? 150 150 Brianne Moore

With the growing use of exome and genome sequencing in research and diagnosis, the ACMG has recently released a policy update on the reporting of secondary findings.

Genomic sequencing is instrumental in identifying many diseases. It can also reveal disease causing variants in our genetic code unrelated to the reason the clinical exome or genome sequencing was performed. These revelations are called secondary findings, and clinicians often grapple with when and how to disclose them to patients.

In 2016, the American College of Medical Genetics and Genomics (ACMG) updated their 2013 minimum list of genes with known or expected pathogenic variants to be reported as secondary findings. The policy update, published in Genetics in Medicine, has added four genes and removed one from this list for a total of 59 genes recommended for return in clinical genomic sequencing.

“Our intent was that this would be a living document with changes and additions dictated by the science and our evolving understanding of genes and disease in populations,” says Gail Herman, MD, PhD, principal investigator for the Center for Molecular and Human Genetics at Nationwide Children’s Hospital, past-president of ACMG and an author on the manuscript.

The genes included on both the original and updated lists adhere to standardized criteria, including prevalence of the disorder, likelihood of severe symptoms (penetrance) and the effectiveness of current treatment options.

According to Dr. Herman, the list is focused on catching genetic disorders early, before symptoms occur, to manage treatment aimed to prevent or significantly reduce morbidity and mortality. The genes chosen were rigorously reviewed and are considered “medically actionable.”

The four newly-added genes are associated with varied clinical features such as potentially fatal neonatal hyperammonemia and autosomal recessive Wilson disease. Currently, no widespread screening for these disorders exists in the general population, and early detection can greatly reduce morbidity rates. All of them have significant risk for premature death if left untreated. Given the severity of these disorders, the ACMG has expanded nomination power to health care professionals outside of genomics.

“It is critical that the input and expertise of our colleagues in other medical specialties are included in this effort. They may be asked to evaluate individuals with a significant secondary finding to determine their disease risk and to supervise their medical surveillance. The development of a tested, standardized gene submission form should enable clinicians of all specialties to have a voice in the process going forward,” adds Dr. Herman.

The ACMG plans for the list to be updated annually to serve as a reference point for initiatives that apply genetic and genomic testing in public health programs as well as in population screenings. It has already been utilized in research to evaluate the efficiency of newborn screening panels in detecting genetic diseases.


Kalia SS et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genetics in Medicine. 2016 Nov 17. Epub ahead of print.

About the author

Brianne is interning as a science writer and editor for Clinical & Research Communications at Nationwide Children's Hospital. She contributes to a variety of publications, including Pediatrics Nationwide and PediatricsOnline.