Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

CREBBP : Rubinstein-Taybi Syndrome

MONDO:0019188 | ORPHA:783 | OMIM:180849
Mode of Inheritance: Autosomal dominant inheritance (HP:0000006)
SOP: Gene Clinical Validity Standard Operating Procedures (SOP), Version 5

Genetic Evidence
Case-Level Data
Evidence Type Case Information Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Variant Evidence
Autosomal Dominant or X-linked Disorder Variant is de novo 2 0-3 12
14.00
12
Schorry EK et al. 2008 Oct 1 (PMID:18792986); Kalkhoven E et al. 2003 Feb 15 (PMID:12566391); Coupry I et al. 2002 Jun (PMID:12070251); Murata T et al. 2001 May 1 (PMID:11331617);
Proband with predicted or proven null variant 1.5 0-2 10 0.00
Proband with other variant type with some evidence of gene impact 0.5 0-1.5 7
0.50
0.5
Schorry EK et al. 2008 Oct 1 (PMID:18792986);
Autosomal Recessive Disease Two variants in trans and at least one de novo or a predicted/proven null variant 2 0-3 12
0.00
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5
0.00
Segregation Evidence Evidence of segregation in one or more families   Sequencing Method 0-3 3
0.00
 
Total LOD Score Canditate Gene Sequencing Exome/Genome or all genes sequenced in linkage region  
2-2.99 0.5 1
3-4.99 1 2
≥5 1.5 3
Case-Control Data
Case-Control Study Type Case-Control Quality Criteria Guidelines Scores PMIDs/Notes
Points/Study Max Points Tally
Single Variant Analysis 1. Variant Detection Methodology
2. Power
3. Bias and confounding
4. Statistical Significance
0-6 12
0.00
Aggregate Variant Analysis 0-6
0.00
Total Genetic Evidence Points (Maximum 12) 12
Experimental Evidence
Evidence Category Evidence Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Function Biochemical Function 0.5 0 - 2 2
2.50
2
Kalkhoven E et al. 2003 Feb 15 (PMID:12566391); Murata T et al. 2001 May 1 (PMID:11331617);
Protein Interaction 0.5 0 - 2 0.00
Expression 0.5 0 - 2 0.00
Functional Alteration Patient cells 1 0 - 2 2
0.00
Non-patient cells 0.5 0 - 1 0.00
Models Non-human model organism 2 0 - 4 4 2.00 4
Tanaka Y et al. 1997 Sep 16 (PMID:9294190);
Cell culture model 1 0 - 2 0.00
Rescue Rescue in human 2 0 - 4
0.00
Rescue in non-human model organism 2 0 - 4
2.00
Bourtchouladze R et al. 2003 Sep 2 (PMID:12930888);
Rescue in cell culture model 1 0 - 2 0.00
Rescue in patient cells 1 0 - 2 0.00
Total Experimental Evidence Points (Maximum 6) 6

 


 

Assertion criteria Genetic Evidence (0-12 points) Experimental Evidence
(0-6 points)
Total Points
(0-18)
Replication Over Time (Y/N)
Description Case-level, family segregation, or case-control data that support the gene-disease association Gene-level experimental evidence that support the gene-disease association Sum of Genetic & Experimental
Evidence
> 2 pubs w/ convincing evidence over time (>3 yrs)
Assigned Points 12 6 18 YES
CALCULATED CLASSIFICATION LIMITED 1-6
MODERATE 7-11
STRONG 12-18
DEFINITIVE 12-18 AND replication over time
Valid contradictory evidence (Y/N)*
NO
CALCULATED CLASSIFICATION (DATE)
DEFINITIVE
02/26/2018
EXPERT CURATION (DATE)
DEFINITIVE
02/21/2018