Exome & Genome Sequencing Suggested for Certain Patients
A recent study published by the American College of Medical Genetics and Genomics (ACMG) has recently suggested exome sequencing (ES) and genome sequencing (GS) as strong first- or second-tier tests, for patients with congenital anomalies, developmental delays, or intellectual disabilities.
What is the ACMG?
- The American College of Medical Genetics and Genomics, also known as
ACMG, founded in 1991
- The “only nationally recognized interdisciplinary professional membership organization,” dedicated and pertaining to improving health through means of medical genetics and/or genomics
- Collaborated with the Association for Molecular Pathology (AMP) in 2015
- Widely-considered to be global leader and prominent authoritative figure within field of medical genetics and genomics
- Pertaining to clinical research, general education, and medical community
- Used by high percentage of clinical laboratories which perform genetic testing, worldwide
What are the ACMG Guidelines and who uses them?
- Created in collaboration with the Association for Molecular Pathology (AMP)
- Serves as a definitive framework for various aspects of clinical genetic testing
- Recommendations are meant to apply to various breadths of genetic testing
- Applies standard terminology as descriptors for Mendelian disorders (both common and rare)
Which type of patients apply to this study?
- The ACMG has strongly recommended the use of ES/GS for patients with the following symptoms: 
- Multiple congenital anomalies (CA)
- Developmental delay (DD)
- Intellectual disability (ID)
- Such symptoms may have potential to be aligned with rare genetic diseases
|Analytical framework of ES/GS for CA/DD/ID patients, figure courtesy of ACMG|
I’m not in that group. What does the study mean for me?
- Potential for systematic evidence review (SER) being applied to various verticals of patients
- Ultimately, this means a wider range of symptoms applicable for ES/GS
- Potential to open up analytical framework (shown above) for wider spectrum of applicable patients, not just CA/DD/ID
Current vs. Suggested
- ACMG suggests CMA as a first-line test for patients with symptoms which align with CA/DD/ID rare genetic diseases
- Recent studies show diagnostic rate ranging from 16-28%
- ACMG suggests ES/GS as a first-line test for patients with symptoms which align with CA/DD/ID rare genetic diseases
- Recent studies show diagnostic rate ranging from 28-68%
- Another study using a similar vertical of patients concluded WES “provides strong evidence for increased diagnostic and clinical utility”
- Study focuses on infants with suspected and potentially rare monogenic conditions
- Yet another study posits a 57% diagnosis rate using WES, compared to 13.5% with standard care
- Study focuses on children with suspected and potentially rare monogenic conditions
ES or GS: Which test is right for me?
- Check out our last two guides, which may help you determine which test is best for you:
- How Does WES Compare to Traditional Methods?
- Comparing proband and trio Whole Exome Sequencing
- Remember to always consult with your licensed physician to select the best test for your situation/condition(s)
- ACMG Homepage
- Standards and guidelines for the interpretation of sequence variants
- ACMG Mission Statement
- ACMG Guideline for ES/GS for patients …
- ACMG Publishes its First Evidence-based Clinical Guideline
- ACMG Recommends Sequencing as Test for Children With Intellectual Disability, Congenital Anomalies
- A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders
- Diagnostic Impact and Cost-effectiveness of Whole-Exome Sequencing for Ambulant Children With Suspected Monogenic Conditions