Appendix 7. Predicted Class for Variants (Opal Pipeline 4.3.2 and below)

Charlene Son-Rigby -

Samples annotated with Opal Pipeline 4.3.2 and below include the Predicted Class field in the variant annotations.

The Predicted Class is computed using rules based on the 2008 American College of Medical Genetics and Genomics (ACMG) guidelines (Richards et al., 2008).

Note: In cases where ClinVar contains multiple submissions with conflicting classifications, the ClinVar classification is not used in Predicted Class assignment.

 

CategoryRule for Predicted Class
Category 1 - Pathogenic
  • Variants classified in ClinVar as pathogenic, and a MAF < 5%
Category 2 - Likely Pathogenic
  • Severe variants in a known disease gene (as defined in OMIM)
    • Stop-gained
    • Stop-lost
    • Frame-shift deletion/insertion/substitution
    • Splice-site [AG/GT]
Category 3A – Uncertain Significance*
  • Any protein changing variant in a known disease gene (as defined in OMIM)
Category 3B - Uncertain Significance
  • Any protein changing variants that are not Category 1, 2, or 3A
Category 4 - Likely Benign
  • Variants with MAF > 5%
  • Synonymous coding variants
  • 5’ and 3’ UTR variants
  • Variants in non-coding genes
  • Intronic variants excluding splice consensus
  • Intergenic variants (excluding upstream and downstream)
Category 5 - Benign
  • Variants classified in ClinVar as Benign, if they are not severe variants as defined in Category 2 (Opal 4.0 Variant Reports)
  • Not used in Opal 3.0 Variant Reports
Category 6 - Disease Associated
  • Variants classified in ClinVar as Disease Associated (Opal 4.0 Variant Reports)
  • Not used in Opal 3.0 Variant Reports

 

References

Richards, C.S., Bale, S., Bellissimo, D.B., Das, S., Grody, W.W., Hegde, M.R., Lyon, E., and Ward, B.E. (2008). ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genetics in Medicine 10, 294–300.

 

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