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Table 2 In-silico predictions (variant analysis report)*

From: Classic Cornelia de Lange syndrome with variant of unknown significance detected in NIPBL gene mutation: a case report

S.No Variant Annotation Tools Categorical Description Database Result
1. Sort Intolerated From Tolerated (SIFT) D: Deleterious (SIFT score ≤ 0.05);
T: Tolerated (SIFT score >0.05)
DbSNP Deleterious (SIFT score = 0.01)
2. Polymorphism Phenotyping v2 (Poly Phen v2) D: Probably damaging (pp2_score ≥ 0.957),
P: Possibly damaging (0.453 ≤ pp2_score ≤ 0.956)
B: Benign (pp2_score ≤ 0.452)
PDB, DSSP, HumDiv, HumVar Possibly damaging (pp2_score = 0.92)
3. Mutation Taster A: Disease_causing_automatic;
D: Disease_causing;
N: Polymorphism [probably harmless];
P: Polymorphism_automatic [known to be harmless]
dbSNP / TGP / ClinVar / HGMD Disease causing
4. Mutation Assessor H: High;
M: Medium;
L: Low;
N: Neutral.
OMIM, Uniprot, Refseq, Pfam, dbSNP Medium
5. Functional Analysis Through Hidden Markov Models (FATHMM V2.3) D: Deleterious (FATHMM score > 0.5);
T: Tolerated ( FATHMM score < 0.5);
HGMD, SwissProt/TrEMBL Deleterious (FATHMM_score = 0.99418)
6. Combined Annotation Dependent Depletion (CADD) Pathogenic ; (>20)
Likely pathogenic; (>15)
Likely benign; (<15)
Benign (<10)
1000 Genomes, Ensembl Pathogenic (CADD_Score = 28.2)
7. Mendelian Clinically Applicable Pathogenicity (M-CAP) Pathogenic; (>0.025), Benign (<0.025) Ensembl Pathogenic (M-CAP_score = 0.721)
8. Likelihood Ratio Test (LRT) D: Deleterious; N: Neutral; U: Unknown HGMD Deleterious
9. Protein Variation Effect Analyzer (PROVEAN) Deleterious < -2.5
Neutral > -2.5
Uniprot Deleterious (Provean_score = -4.1)
10. CONsensusDELeteriousness (Condel) D: Deleterious (1.0)
N: Neutral (0.0)
Ensembl Deleterious
11. Variant Effect Predictor (VEP) HIGH; MODERATE; LOW Ensembl HIGH
  1. Abbreviations: dbSNP: Database of Single Nucleotide Polymorphisms, pp2_score: PolyPhen2_score, PDB:  Protein Data Bank, DSSP:  Dictionary of Secondary Structure in Proteins, TGP:  Thousand Genome Project, HGMD:  Human Genome Mutation Database, OMIM:  Online Mendelian Inheritance In Man, Refseq:  Reference Sequence Database, Pfam:  Database of Protein families, TrEMBL:  Translated European Molecular Biology Laboratory
  2. *Using ACMG Guidelines, 2015 [10]