Table 1

Probability calculations for attaining (A) evidence elements and (B) classification categories

Evidence strengthOdds of pathogenicityExponent score
Very Strong (VS)3502.088 8
Strong (S)18.72.084 4
Moderate (M)4.332.082 2
Supporting (P)2.082.081 1
Classification categoryPrior probabilityCombined odds of pathogenicityExponent sumPosterior probability
Pathogenic0.11514 (2.08+10)≥100.99
Likely pathogenic81 (2.08+6)6–90.90
Likely benign0.48 (2.08−1)(−1)−(−5)0.05
Benign0.01 (2.08−6)≤−60.001*
  • *The posterior probability attained with an exponent sum of −6 has been rounded down to 0.001, consistent with the UK Association for Clinical Genomic Science Best Practice Guidelines for Variant Classification in Rare Disease 2020.4