SUMMARY:

New DNA technologies make screening for genetic conditions in the general population possible. ACMG has delineated ‘points to consider’ prior to initiating broad population-based screening. While such screening programs hold the potential to improve general population health, identification of disease risk is of benefit if coupled with “evidence based risk reducing clinical care.”

KEY POINTS:

• ACMG ‘secondary findings’ should not be used for screening purposes
  • ACMG has a list of 59 genes and 30 conditions that should be reported, even if the initial genetic test requisition was for another unrelated disorder  
  • This list was created because these specific genes and disorders are medically actionable, for example, pathogenic BRCA1 mutations
  • In theory, one could make the case for screening everyone for these disorders but broad based screening for secondary findings is not a viable cost- effective option for the population at large
• DNA-based screening should not replace diagnostic assessment
  • Individuals with a personal or family history of disease are at increased risk and need diagnostic testing, not a screening test
  • Limited DNA based-screening can do more harm than good for this population
  • Example: A negative screening BRCA1/2 result that only looks for common variants in an individual with significant family history of breast and ovarian cancer may miss the causative variant, thus giving a false sense of security for a “screened negative individual.”
• Disease risks identified through screening should not include DNA variants of uncertain significance (VUS)
  • ACMG has set forth five categories of genetic variant interpretation: Benign (B), Likely Benign (LB), Variant of Uncertain Significance (VUS), Likely Pathogenic (LP), and Pathogenic (P)
  • Over time, a VUS may be upgraded to likely pathogenic or downgraded to likely benign
  • In an effort to promote risk-reducing care, only pathogenic and likely pathogenic variants should be reported
• DNA-based screening should be linked to evidence-based clinical care pathways
  • A key requirement for population based screening is that follow-up be made available following screening
  • If an individual has a positive screening test but does not have access to follow-up care, there can be no improvement in health outcomes
• Follow-up for DNA-based screening should be consistent with best practices and professional guidelines
  • Expect guidelines to change as knowledge expands 
• Organizations involved in DNA-based screening are expected to participate in data-sharing
  • All data should be de-identified
• DNA-based screening that have proven benefits across populations should be offered to everyone
  • Critical to promote health-care equity and limit health disparities
  • Newborn screening (NBS) serves as a model program
  • Collaboration harnesses the power of state-driven public health initiatives

Learn More – Primary Sources:

DNA-based screening and population health: a points to consider statement for programs and sponsoring organizations from the American College of Medical Genetics and Genomics (ACMG)

Related ObG Topics:

The Exome and Whole Exome Sequencing: Prenatal Testing Recommendations

ACOG Opinion on Expanded Carrier Screening

Newborn Screening: NBS Basics for Healthcare Professionals