Evidence of pathogenicity :
Evidence of benign impact :
Combined significance :

  Benign Pathogenic
Strong (BS) Supporting (BP) Supporting (PP) Moderate (PM) Strong (PS) Very Strong (PVS)

Pathogenic
(i) 1 Very strong (PVS1) AND
 (a) ≥1 Strong (PS1-PS4) OR
 (b) ≥2 Moderate (PM1-PM6) OR
 (c) 1 Moderate (PM1-PM6) and 1 supporting (PP1-PP5) OR
 (d) ≥2 Supporting (PP1-PP5)
(ii) ≥2 Strong (PS1-PS4) OR
(iii) 1 Strong (PS1-PS4) AND
 (a) ≥3 Moderate (PM1-PM6) OR
 (b) 2 Moderate (PM1-PM6) AND ≥2 Supporting (PP1-PP5) OR
 (c) 1 Moderate (PM1-PM6) AND ≥4 supporting (PP1-PP5)
Likely pathogenic
(i) 1 Very strong (PVS1) AND 1 moderate (PM1-PM6) OR
(ii) 1 Strong (PS1-PS4) AND 1-2 moderate (PM1-PM6) OR
(iii) 1 Strong (PS1-PS4) AND ≥2 supporting (PP1-PP5) OR
(iv) ≥3 Moderate (PM1-PM6) OR
(v) 2 Moderate (PM1-PM6) AND ≥2 supporting (PP1-PP5)
(vi) 1 Moderate (PM1-PM6) AND ≥4 supporting (PP1-PP5)
Benign
(i) 1 Stand-alone (BA1) OR
(ii) ≥2 Strong (BS1-BS4)
Likely benign
(i) 1 Strong (BS1-BS4) and 1 supporting (BP1-BP7) OR
(ii) ≥2 Supporting
Uncertain significance
(i) Other criteria shown above are not met OR
(ii)the criteria for benign and pathogenic are contradictory️

This page is a partial implementation of an article of
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in medicine. 2015 Mar 5;17(5):405-23. PDF

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