Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

CEP78 : Cone-rod dystrophy and hearing loss

HGNC:25740 | OrphaNet: | OMIM:617236
Mode of Inheritance: Autosomal recessive inheritance (HP:0000007)

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
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 8.0 8
de Castro-Miró M et al. 2016 (PMID:28005958); Nikopoulos K et al. 2016 Sep 1 (PMID:27588451); Namburi P et al. 2016 Sep 1 (PMID:27588452); Fu Q et al. 2017 Mar (PMID:27627988);
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 3.0 3
Fu Q et al. 2017 Mar (PMID:27627988); Nikopoulos K et al. 2016 Sep 1 (PMID:27588451);
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) 11
Experimental Evidence
Evidence Category Evidence Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Function Biochemical Function 0.5 0 - 2 2 1.5 1.5
Nikopoulos K et al. 2016 Sep 1 (PMID:27588451); Namburi P et al. 2016 Sep 1 (PMID:27588452);
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2
Functional Alteration Patient cells 1 0 - 2 2
Non-patient cells 0.5 0 - 1
Models & Rescue Animal model 2 0 - 4 4
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) 1.5

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 11 1.5 12.5 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)
STRONG
12/27/2016
EXPERT CURATION (DATE)
STRONG
04/12/2017
Reviewed by the ClinGen Hearing Loss Working Group