Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

DNM1 : Infantile Epilepsy Syndrome

HGNC:2972 | OrphaNet: ORPHA1934 | OMIM:602377
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
18.0
12
EuroEPINOMICS-RES Consortium. et al. 2014 Oct 2 (PMID:25262651); Nicita F et al. 2015 May (PMID:25779878); Allen AS et al. 2013 Sep 12 (PMID:23934111); Nakashima M et al. 2016 Jan (PMID:26611353); Allen NM et al. 2016 Jan (PMID:26648591); Helbig KL et al. 2016 Sep (PMID:26795593);
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
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) 12
Experimental Evidence
Evidence Category Evidence Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Function Biochemical Function 0.5 0 - 2 2 1.0 1
van der Bliek AM et al. 1993 Aug (PMID:8101525);
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2
Functional Alteration Patient cells 1 0 - 2 2 1.0 1
Dhindsa RS et al. 2015 Jun (PMID:27066543);
Non-patient cells 0.5 0 - 1
Models & Rescue Animal model 2 0 - 4 4 2.5 2.5
Asinof SK et al. 2015 Jun (PMID:26125563); Boumil RM et al. 2010 Aug 5 (PMID:20700442);
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) 4.5

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 4.5 16.5 YES
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)
DEFINITIVE
12/12/2016
EXPERT CURATION (DATE)
DEFINITIVE
12/13/2016