Skip to main content

Conference Program

Subpage Hero

Loading

Survey results reveal barriers and solutions to the use of functional data in variant interpretation

Laboratory Genetics and Genomics
  • Primary Categories:
    • Laboratory Genetics
  • Secondary Categories:
    • Laboratory Genetics
Introduction:
Functional evidence is a valuable tool for interpreting variants of uncertain significance (VUS). ACMG/AMP have included guidance for using functional evidence (PS3/BS3) in their clinical variant interpretation guidelines. However, the usage of functional evidence and guidelines by clinical and research geneticists and genetic counselors is currently unknown.

Methods:
With the goal of better understanding functional data usage in the clinical genetics community, an online survey was developed and distributed to members of the NSGC, AMP, ACMG, ClinGen, ABMGG, the AVE Alliance, and the UK’s NHS. Members who are actively engaged in clinical variant interpretation were eligible to participate.

Results:
190 individuals who responded to the survey were eligible. The three most common positions held by respondents were ABMGG certified laboratory medical geneticists (23.2%), variant review scientist (22.6%), and clinical medical geneticists (17.9%). The median respondent reported 11-20 years-of-experience. A majority of the respondents reported interpreting more than 100 variants per year (71.6%), with 26.8% reporting reinterpreting more than 26 variants per year. 80.5% of responders reported that insufficient data was frequently the cause for classifying variants as VUSs. Overall, 78.4% of respondents reported engaging with functional evidence and most (77.4%) evaluating functional data for variant classification in the clinical setting. More than half of the respondents reported functional data was rarely or never available for their variants of interest (67.4%). A majority (90.5%) of respondents considered insufficient quality metrics or confidence in the accuracy of functional data to be a barrier to using functional evidence. When asked about options of interventions that could improve use of functional evidence, almost half of the respondents noted access to primary functional data (42.6%), and standardized interpretation of functional data through ClinVar (45.8%) would significantly improve their use.

Conclusion:
Overall, the results of this study provided insights on the functional evidence usage for individuals involved in variant interpretation. It also showed a demand for a robust database that provides more accessible information on the quality and accuracy of functional evidence to promote use of functional evidence in variant interpretation.

Agenda

Sponsors