Table 2.
In silico analysis to predict the effect of the variants identified in the ABCC8 gene.
| cDNA and protein position | Annovar impact | CADD | Sift | Polyphen2 | MutAssesor | Fathmm | VEST | Score | ACMG Classification |
|---|---|---|---|---|---|---|---|---|---|
| c.211C > T p.(His71Tyr): | – | Damaging | Damaging | Probably damaging | Damaging | Damaging | Damaging | 5.5/7 | Likely pathogenic |
| c.298G > A p.(Glu100Lys) | MODERATE | Possibly damaging | Benign | Benign | Benign | Damaging | Possibly damaging | 2.5/7 | VUS |
| c.1429G > A p.(Val477Met) | MODERATE | Damaging | Damaging | Damaging | Possibly damaging | Damaging | Damaging | 6/7 | Likely pathogenic |
| c.1643C > T p.(Thr548Met) | MODERATE | Damaging | Damaging | Damaging | Possibly damaging | Damaging | Possibly damaging | 5.5/7 | Likely pathogenic |
| c.2176G > A p.(Ala726Thr) | MODERATE | Damaging | Benign | Benign | Benign | Damaging | Benign | 2.5/7 | VUS |
| c.2422C > A p.(Gln808Lys) | MODERATE | Damaging | Possibly damaging | Probably damaging | Benign | Damaging | Damaging | 4.5/7 | Likely pathogenic |
| c.2694 + 1G > A | – | Damaging | – | – | – | – | – | 1/7 | Likely pathogenic |
| c.3238G > A p.(Val1080Ile) | MODERATE | Damaging | Benign | Benign | Benign | Damaging | Benign | 2.5/7 | VUS |
| c.3288_3289del p.(His1097ProfsTer16) | HIGH | – | – | – | – | – | – | 1/7 | Pathogenic |
| c.3394G > A p.(Asp1132Asn) | MODERATE | Damaging | Damaging | Damaging | Damaging | Damaging | Possibly damaging | 6/7 | Pathogenic |
| c.3976G > A p.(Glu1326Lys) | MODERATE | Damaging | Possibly damaging | Benign | Benign | Damaging | Damaging | 4/7 | Likely pathogenic |
| SMAD1 c.27delinsGTAAAG p.(Phe9LeufsTer2) | – | – | – | – | – | – | – | – | Likely pathogenic |
CADD ranges: s > 14 damaging, s in [11,14) possibly damaging, SIFT ranges: benign s > 0.23, possibly damaging s in (0.06, 0.23), damaging s ≤ 0.06. Polyphen2 ranges: benign s < 0.03, possibly damaging s in (0.03, 0.3), damaging s > 0.3. MutAssesor ranges: benign s < 1.12, possibly damaging s in [1.12, 1.8), damaging s > 1.8. Vest ranges: Benign s < 0.17, possibly damaging s in [0.17, 0.65), damaging s ≥ 0.65.