Table 1

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

Evidence strengthOdds of pathogenicityExponent score
Very Strong (VS)3502.0888
Strong (S)18.72.0844
Moderate (M)4.332.0822
Supporting (P)2.082.0811
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