Gene Validity Classification Summary

Gene/Disease Pair:

COL2A1 : Spondyloepiphyseal dysplasia (Stanescu type)

HGNC:2200 | OrphaNet: N/A | OMIM:616583
Mode of Inheritance: Autosomal dominant inheritance (HP:0000006)

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
2.0
2
Jurgens J et al. 2015 Oct (PMID:26183434);
Proband with predicted or proven null variant 1.5 0-2 10
Proband with other variant type with some evidence of gene impact 0.5 0-1.5 7 1.0 1
Jurgens J et al. 2015 Oct (PMID:26183434); Hammarsjö A et al. 2016 Jan (PMID:26420734);
Autosomal Recessive Disease Two variants in trans and at least one de novo or a predicted/proven null variant 2 0-3 12
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5
Segregation Evidence Evidence of segregation in one or more families LOD Score Examples 3 5 0-7 7
2 4
1.5 3
1 1.5
   
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
Aggregate Variant Analysis 0-6 12
Total Genetic Evidence Points (Maximum 12) 3
Experimental Evidence
Evidence Category Evidence Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Function Biochemical Function 0.5 0 - 2 2
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2
Functional Alteration Patient cells 1 0 - 2 2 2.0 2
Chan D et al. 1993 Jul 15 (PMID:8325895); Vandenberg P et al. 1991 Sep 1 (PMID:1881905); Garofalo S et al. 1991 Nov 1 (PMID:1946380);
Non-patient cells 0.5 0 - 1
Models & Rescue Animal model 2 0 - 4 4 4.0 4
Vandenberg P et al. 1991 Sep 1 (PMID:1881905); Garofalo S et al. 1991 Nov 1 (PMID:1946380);
Cell culture model system 1 0 - 2
Rescue in animal model 2 0 - 4
Rescue in engineered equivalent 1 0 - 2
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 3 6 9 NO
CALCULATED CLASSIFICATION LIMITED 1-6
MODERATE 7-11
STRONG 12-18
DEFINITIVE 12-18 AND replication over time
Valid contradictory evidence (Y/N)*
CALCULATED CLASSIFICATION (DATE)
MODERATE
05/25/2016
EXPERT CURATION (DATE)
MODERATE
12/01/2016