Table 1.
In silico analysis results and allele frequencies of putatively damaging FREM2 and FRAS1 alleles
| Allele (FREM2 = NM_207361.5 FRAS1 = NM_025074.6) | PolyPhen-2 HumDiv and HumVar, SIFT, MutationTaster |
Ethnically-matched allele frequency |
|||
|---|---|---|---|---|---|
| CDH cohort | NHLBI Exome Variant Server | ExAC Database | gnomAD | ||
| FREM2 c.4031G>A, p.Arg1344His | P, B, T, DC | European American 3/60 (5%) | European American 23/8600 (0.27%), Homo = 0, P < 0.001 | Non-Finnish Europeans 240/66714 (0.36%); Homo = 1, P < 0.0001 | Non-Finnish Europeans 494/126670 (0.39%), Homo = 1, P < 0.01 |
| Finnish Europeans 37/6614 (0.56%), Homo = 0, P < 0.01 | Finnish Europeans 140/25786 (0.54%), Homo = 1, P < 0.01 | ||||
| FREM2 c.4558C>T, p.Arg1520Trp | PD, PD, D, DC | European American 1/60 (1.67%) | European American 5/8600 (0.058%), Homo = 0, P < 0.05 | Non-Finnish Europeans 2/66634 (0.003%), Homo = 0, P <0.0001 | Non-Finnish Europeans 11/125910 (0.009%), Homo = 0, P < 0.01 |
| Finnish Europeans 0/6614 | Finnish Europeans 0/25790 | ||||
| FREM2 c.5938_5940delCTT, p.Leu1981del | NA, NA, NA, DC | NA | Allele not detected in any ethnic group | Allele not detected in any ethnic group | South Asian 7/30778 (0.023%), Homo = 0 |
| FREM2 c.4994C>T, p.Ser1665Phe | P, P, T, P | Filipino 1/2 (50%) | Allele not detected in any ethnic group | Allele not detected in any ethnic group | Allele not detected in any ethnic group |
| FRAS1 c.2389G>A, p.Glu797Lys | P, B, T, P | European Americans 1/60 (1.67%) | Allele not detected in European Americans | Non-Finnish European 1/66724 (0.0015%), Homo = 0, P < 0.0001 | Non-Finnish Europeans 6/111578 (0.005%), Homo = 0, P < 0.01 |
| Finnish European 0/6614 | Finnish European 0/22296 | ||||
| FRAS1 c.9806G>A, p.Arg3269Gln | PD, PD, D, DC | European Americans 1/60 (1.67%) | European Americans 83/8458 (0.98%), Homo = 0, P = 0.45 | Non-Finnish European 584/65864 (0.83%), Homo = 3, P = 0.415 | Non-Finnish European 1188/125176 (0.95%), Homo = 8, P = 0.325 |
| Finnish European 30/6614 (0.45%), Homo = 0, P = 0.245 | Finnish European 99/25568 (0.39%), Homo = 0, P = 0.186 | ||||
| FRAS1 c.6323A>T, p.Asp2108Val | P, B, D, DC | Filipino 1/2 (50%) | Allele not detected in any ethnic group | Allele not detected in any ethnic group | Allele not detected in any ethnic group |
B, benign; D, damaging; DC, disease causing; NA, not applicable; P, possibly damaging; PD, probably damaging; T, tolerated.