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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]