Table 1b. Criteria for variant classification.

The evidence available about each variant was combined to determine its likely effect and likelihood of causing disease

Pathogenicity	Algorithm
Deleterious	Found in patient(s) and not controls OR in significant excess in patients AND seen on gnomAD at less than 1 in 50,000; AND Pathogenic Strong evidence 1) OR 2), PLUS one additional Pathogenic Strong or two Pathogenic moderate or one Pathogenic moderate and one Pathogenic Supporting criterion
Likely deleterious	The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls, or only seen on gnomAD at less than 1 in 10,000; AND Pathogenic Moderate evidence 1) OR 2) OR 3) AND one additional Pathogenic Strong or Moderate or Supporting criteria.
Possibly deleterious	Found on gnomAD at less than 1 in 5000 and at least one Supporting criterion
Uncertain	Insufficient or conflicting evidence Missense mutation not nearby other missense mutations thought to be pathogenic
Likely benign	One Benign Strong criteria OR one Benign Moderate AND one Benign Supporting criteria OR two Benign Supporting criteria
Benign	Benign Independent OR one Benign Strong evidence criterion AND two further Benign Moderate or Benign Supporting criteria
Risk factor	Previously reported as risk factor, either variant itself or clear established pattern in gene, AND >1 in 10000 in gnomAD; AND the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls