Table 2. Penetrance of Mild ABCA4 Alleles When Accompanied by a Severe ABCA4 Allele.
| Variable in calculation | c.5882G>A | c.5714+5G>A | c.6089G>A | c.3113C>T | c.2588G>C |
|---|---|---|---|---|---|
| LOVD (cases) | |||||
| Observed number of patients with mild/severe genotype | 177 | 30 | 21 | 36 | 80 |
| Frequency of mild/severe genotypea | 0.087149 | 0.014771 | 0.010340 | 0.017725 | 0.039389 |
| gnomAD (controls) | |||||
| AF mild variant | 0.003778 | 0.000550 | 0.000620 | 0.002302 | 0.007840 |
| Sum AF severe variants | 0.002290 | 0.002290 | 0.002290 | 0.002290 | 0.002290 |
| Frequency of mild/severe genotypeb | 0.000017 | 0.000003 | 0.000003 | 0.000011 | 0.000036 |
| Penetrance | 50.4% | 58.6% | 36.4% | 16.8% | 11.0% |
Abbreviations: AF, allele frequency; gnomAD, Genome Aggregation Database; LOVD, Leiden Open Variation Database.
a
The observed number of patients in LOVD with a mild variant in combination with a severe variant was divided by 2031, the total number of non-Finnish European patients with at least 2 ABCA4 variants in LOVD.
b
The expected frequency of the mild variant in combination with a severe variant in the general population was obtained by 2 × mild AF × sum severe AF (Hardy-Weinberg principle).