Wednesday, July 7, 2021

Very Brief Blog: ACMG Publishes Guideline for Exome, Genome Sequencing in Pediatrics

The American College of Medical Genetics and Genomics (ACMG) has released its first evidence-based guideline for clinical practice using exome/genome testing.  The guideline focuses on (1) congenital anomalies and (2) intellectual disability.

  • See the press release here.
  • See the 9-page guideline Manickam et al. here.
  • See coverage at Genomeweb, July 1, here.
The new guideline summarizes,
"The literature supports the clinical utility and desirable effects of ES/GS [exome, genome sequencing] on active and long-term clinical management of patients with CA/DD/ID, and on family-focused and reproductive outcomes with relatively few harms. Compared with standard genetic testing, ES/GS has a higher diagnostic yield and may be more cost-effective when ordered early in the diagnostic evaluation."
The report notes that exome sequencing does not capture certain types of variants including copy number variants, while stating that "genome sequencing provides coverage of both array and exome targets."  I have always been puzzled by payers who happily cover exome + microarray together, but decline to cover one test for sequence and copy number ouput (genome) even when it is the same or lower cost.

Previously, ACMG had had a "microarray" guideline for constitutional analysis in congenital anomalies and intellectual disability (here).  A March 2020 Ontario Health Technology Assessment recommended exome testing as a second-tier test, that is, to be positioned as a reflex test after a full microarray test had come back negative (here).

See also a new Avalere paper on the tortuous "diagnostic journey" for new rare disease patients, here.