Table 3.
Allele frequency cutoffs for dominant and recessive hearing loss disorders.
| ACMG-AMP Criteria | MAF | Preval. | Allelic Het.† | Penetrance | |
|---|---|---|---|---|---|
|
AUTOSOMAL RECESSIVE |
BA1 |
≥0.005 (0.5%) |
1/200 |
7.2% |
100% |
| BS1 | ≥0.003 (0.3%) |
1/200 |
4.4% | 100% | |
| BS1_Supporting |
≥0.0007 (0.07%) |
1/200 |
1.0% |
100% | |
| PM2_Supporting |
<0.0007 (0.07%) |
Can apply PM2_Supporting if MAF is < BS1_Supporting (0.07%) |
|||
| PM2 | ≤0.00007 (0.007%) |
Can apply PM2_moderate if MAF is an order of magnitude below BS1_Supporting (ie ≤0.007%); |
|||
|
AUTOSOMAL
DOMINANT |
BA1 |
≥0.001 (0.1%) |
1/30 |
5% |
80% |
| BS1 |
≥0.0002 (0.02%) |
1/150 |
5% | 80% | |
| PM2 | ≤0.00002 (0.002%) |
Can apply PM2_Moderate if MAF is an order of magnitude below BS1 (ie ≤0.002%); |
|||
Abbreviations: Preval. = Prevalence. Allelic Het. - Allelic heterogeneity.
†
Allelic heterogeneity encompassed both genetic and allelic heterogeneity because allele frequencies were derived from hearing loss cases spanning all genetic etiologies.