Table 4.
Results from the four different bioinformatic programs used to predict the effect of missense, synonymous and intronic changes on the splicing process in the ENG gene (NNSplice, NetGene2, Splice View and HSF Human)
| Sequence variants | Reference | Genotype frequency | NNSplice | NetGene2 | Splice View | HSF Human | Score |
|---|---|---|---|---|---|---|---|
| c.207G>A (p.(L69L)) | rs11545664 | G: 89 % A: 11 % | Neutral | Neutral | Neutral | A new acceptor site is created | 1 |
| c.219+25G>T | This study | ---------- | Neutral | Neutral | Neutral | Neutral | 0 |
| c.360+56T>A | This study | ---------- | Neutral | Score for the main donor site decreases from 93 to 89 | Neutral | A new acceptor site is created | 2 |
| c.498G>A (p.(Q166Q)) | Pousada et al [8] | G: 100 % A: 0 % | Neutral | Score for the main donor site decreases from 90 to 87 | A new donor site is created | Score for the main acceptor site decrease from 82 to 53 | 3 |
| c.572G>A (p.(G191D)) | Rs41322046 (Lesca et al [27]) | G: 100 % A: 0 % | Neutral | Score for the main acceptor site increase from 18 to 19 | Neutral | Neutral | 1 |
| c.775G>A (p.(V259M)) | This study | ---------- | Neutral | Score for the main acceptor site increase from 35 to 37 | Neutral | A new acceptor site is created | 2 |
| c.817+17T>A | This study | ---------- | Neutral | Score for the main donor site decreases from 100 to 99 | Neutral | Score for the main acceptor site decrease from 82 to 78 | 2 |
| c.817+23G>A | This study | ---------- | Neutral | Neutral | Neutral | Neutral | 0 |
| c.991+21_991+26dupCCTCCC | rs148063362 | WT: 74 % DUP: 26 % | Neutral | Neutral | Neutral | Neutral | 0 |
| c.1272+6A>T | This study | ---------- | Neutral | Neutral | A new donor site is created | Score for the main acceptor site decrease from 65 to 37 | 2 |
| c.1295A>T (p.(S432C)) | This study | ---------- | Neutral | Score for the main donor site decreases from 74 to 54 | Neutral | Score for the main acceptor site decrease from 76 to 72 | 2 |
| c.1402G>C (p.(E468Q)) | rs370554511 | G: 100 % C: 0 % | Neutral | Neutral | The WT consensus sequence is not recognized | Score for the main acceptor site increase from 70 to 80 | 1 |
| c.1421 T>A (p.(F474Y)) | This study | ---------- | Neutral | Neutral | Neutral | Score for the main acceptor site decrease from 87 to 85 | 1 |
| c.1633G>A (p.(G545S)) | rs1428896669 (Pfarr et al [7]) | G: 100 % A: 0 % | Neutral | Neutral | Neutral | A new acceptor site is created | 1 |
| c.1660C>A (p.(R554C)) | COSM1105417 | C: 100 % A: 0 % | Neutral | Score for the main donor site decreases from 69 to 67 | Neutral | A new acceptor site is created | 2 |
These results are considered positive if the score is equal or greater than two. The Genotype frequency values were for 1000 Genome Project. For novel mutations, described in this study, no genotype data were available