Table 3 In silico analysis of PDGFRA variations in 55 CRC
Localisation | Sequence variation (nucleotide) | Variant Id dbSNP/Cosmic | Variant type | Protein variation | Frequency | Prediction of variant effect | ClinVar | Phenotype data (ensembl) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Mutation taster/human splicing finder | PROVEAN/ | UMD predictor | ||||||||||
SIFT/ | ||||||||||||
MAF | GenomAD | In our cohort (N = 55 CRC/%) | COSMIC (FATHMM) | |||||||||
Reported variations | ||||||||||||
Intronic (17–18) | c.2440-50_2440-49insA | rs3830355 | Insertion | NA | 0.49 | 0.805 | 53 (96.3%) | Polymorphism/ | NA | NA | NA | NA |
Alteration of WT Branch Point + creation of an intronic ESE site | ||||||||||||
Intronic (17–18) | c.2440-42C > T | rs1218113433 | SNV | NA | < 0.01 | 3.9932e−06 | 20 (36.3%) | Polymorphism/ | NA | NA | NA | NA |
No significant splicing motif alteration detected | ||||||||||||
Intronic (18–19) | c.2562 + 28 G > A | rs767821722 | SNV | NA | < 0.01 | 7.96476e−06 | 1 (1.8%) | Polymorphism/ | NA | NA | NA | NA |
Alteration of an intronic ESS site + Creation of an intronic ESE site (probably no impact on splicing) | ||||||||||||
Intronic (18–19) | c.2562 + 51C > T | rs1242272513 | SNV | NA | < 0.01 | 6.97632e−06 | 1 (1.8%) | Polymorphism:Protein features might be affected + splice site changes/ | NA | NA | NA | NA |
No significant splicing motif alteration detected | ||||||||||||
Exonic | c.2464C > T | COSM5772696/COSV57271399 | Non synonymous Somatic SNV | R822C | NA | NA | 3 (5.4%) | Disease causing:amino acid sequence changed + protein features might be affected + splice site changes/ | Deleterious/ | Pathogenic | NA | Breast Tumor |
Damaging/ | ||||||||||||
No significant splicing motif alteration detected | Pathogenic | |||||||||||
Exonic | c.2464C > A | COSM19324/ COSV57277919 | Non synonymous Somatic SNV | R822S | NA | NA | 2 (3.6%) | Disease causing: amino acid sequence changed + protein features might be affected + splice site changes/ | Deleterious/ | Pathogenic | NA | Soft tissue tumor |
Activation of an exonic cryptic acceptor site, with presence of one or more cryptic branch point(s) | Damaging/ | |||||||||||
Pathogenic | ||||||||||||
Exonic | c.2472C > T | rs2228230/ COSM22413 | Synonymous somatic SNV | V824V | 0.45 | 0.183 | 10 (18.1%) | Polymorphism: protein features might be affected + splice site changes/ | Neutral/ | Polymorphism | Benign | Gastrointestinal stromal tumors, Idiopathic hypereosinophilic syndrome |
Creation of an exonic ESS site | Tolerated/ | |||||||||||
Pathogenic | ||||||||||||
Exonic | c.2517G > T | rs1213039385/COSM6100284 | Synonymous somatic SNV | L839L | < 0.01 | 3.97842e-06 | 1 (1.8%) | Disease causing: protein features might be affected + splice site changes/ | Neutral/ | Polymorphism | NA | Lung tumor |
Tolerated/ | ||||||||||||
Creation of an exonic ESS site + Alteration of an exonic ESE site | Pathogenic | |||||||||||
Unreported variations | ||||||||||||
Intronic (17–18) | g.56700C > T | NA | SNV | NA | NA | NA | 26 (47.2%) | Polymorphism: protein features might be affected + splice site changes/ | NA | NA | NA | NA |
No significant splicing motif alteration detected | ||||||||||||
Intronic (17–18) | g.56701 T > G | NA | SNV | NA | NA | NA | 4 (7.2%) | Polymorphism: protein features might be affected + splice site changes/ | NA | NA | NA | NA |
alteration of an intronic ESS site + Creation of an intronic ESE site (probably no impact on splicing) | ||||||||||||
Intronic (17–18) | g.56717C > G | NA | SNV | NA | NA | NA | 5 (9%) | Polymorphism/ | NA | NA | NA | NA |
Alteration of WT branch point | ||||||||||||
Exonic | c.2514C > T | NA | Synonymous SNV | G838G | NA | NA | 3 (5.4%) | Disease causing/ | Neutral/ | Probably pathogenic | NA | NA |
Activation of an exonic cryptic donor site + Creation of an exonic ESE site | Tolerated/ | |||||||||||
NA | ||||||||||||
Exonic | c.2481A > T | NA | Synonymous SNV | A827A | NA | NA | 5 (9%) | Disease causing: protein features might be affected + splice site changes/ | Neutral/ | Polymorphism | NA | NA |
Tolerated/ | ||||||||||||
No significant splicing motif alteration detected | NA | |||||||||||
Exonic | c.2459C > T | NA | Non synonymous SNV | A820V | NA | NA | 5 (9%) | Disease causing: amino acid sequence changed + protein features might be affected + splice site changes/ | Deleterious/ | Pathogenic | NA | NA |
Activation of an exonic cryptic donor site + Creation of an exonic ESS site + Alteration of an exonic ESE site | Damaging/ | |||||||||||
NA | ||||||||||||
Exonic | c.2496G > A | NA | Synonymous SNV | V832V | NA | NA | 2 (3.6%) | Disease causing: protein features might be affected + splice site changes/ | Neutral/ | Polymorphism | NA | NA |
Creation of an exonic ESS site + Alteration of an exonic ESE site | Tolerated/ | |||||||||||
NA | ||||||||||||
Exonic | c.2520C > A | NA | Synonymous SNV | A840A | NA | NA | 1 (1.8%) | Disease causing: protein features might be affected + splice site changes/ | Neutral/ | Polymorphism | NA | NA |
Creation of an exonic ESS site + Alteration of an exonic ESE site | Tolerated/ | |||||||||||
NA | ||||||||||||
Exonic | c.2507A > T | NA | Non synonymous SNV | D836V | NA | NA | 1 (1.8%) | Disease causing: protein features might be affected + splice site changes/ | Deleterious/ | Pathogenic | NA | NA |
Alteration of an exonic ESE site | Damaging/ | |||||||||||
NA | ||||||||||||
Intronic (18–19) | g.56935G > A | NA | SNV | NA | NA | NA | 2 (3.6%) | Polymorphism/ | NA | NA | NA | NA |
Alteration of an intronic ESS site + Creation of an intronic ESE site (probably no impact on splicing) | ||||||||||||