Gene Validity Curation

ADGRV1 - Usher syndrome type 2

Gene: ADGRV1 (HGNC:17416)
Classification - 02/15/2017
Disease: Usher syndrome type 2 (MONDO_0016484)
Mode of Inheritance: Autosomal recessive inheritance (HP:0000007)
Replication over time: YES Contradictory Evidence: NO
Expert Panel: Hearing Loss EP
Evidence Summary:
Genetic Evidence
Case-Level Data
Evidence Type Case Information Type Guidelines Points PMIDs/Notes
Default Range Max Count Total Counted
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 4
8
9
Moteki H et al. 2015 May (PMID:25743181); Weston MD et al. 2004 Feb (PMID:14740321); Yang J et al. 2016 Apr (PMID:26432996);
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5 1
1
Kahrizi K et al. 2014 Dec (PMID:25572244);
Segregation Evidence   Summed LOD Family Count 0.5 0.5  
Candidate gene sequencing 2.66 2
Kahrizi K et al. 2014 Dec (PMID:25572244); Weston MD et al. 2004 Feb (PMID:14740321);
Exome/genome or all genes sequenced in linkage region
Total Summed LOD Score 2.66    
Case-Control Data
Case-Control Study Type Case-Control Quality Criteria Guidelines Points PMIDs/Notes
Points/Study Max Count Points Counted
Single Variant Analysis 1. Variant Detection Methodology
2. Power
3. Bias and confounding
4. Statistical Significance
0-6 12
Aggregate Variant Analysis 0-6
Total Genetic Evidence Points (Maximum 12) 9.5
Experimental Evidence
Evidence Category Evidence Type Guidelines Points PMIDs/Notes
Default Range Max Count Total Counted
Function Biochemical Function 0.5 0 - 2 2
1
Protein Interaction 0.5 0 - 2 1 0.5
Chen Q et al. 2014 Dec 26 (PMID:25406310);
Expression 0.5 0 - 2 1 0.5
Zallocchi M et al. 2012 Oct 03 (PMID:23035094);
Functional Alteration Patient cells 1 0 - 2 2
Non-patient cells 0.5 0 - 1
Models Non-human model organism 2 0 - 4 4 2 4 4
Yagi H et al. 2007 Feb (PMID:17295842); McGee J et al. 2006 Jun 14 (PMID:16775142);
Cell culture model 1 0 - 2
Rescue Rescue in human 2 0 - 4
Rescue in non-human model organism 2 0 - 4
Rescue in cell culture model 1 0 - 2
Rescue in patient cells 1 0 - 2
Total Experimental Evidence Points (Maximum 6) 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 9.5 5 14.5 YES
CALCULATED CLASSIFICATION LIMITED 1-6
MODERATE 7-11
STRONG 12-18
DEFINITIVE 12-18 AND replication over time
Valid contradictory evidence (Y/N)*
NO
CALCULATED CLASSIFICATION (DATE)
Definitive
02/13/2020
EXPERT CURATION (DATE)
Definitive
02/15/2017