Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

GAA : Glycogen storage disease type II

MONDO:0009290 | ORPHA:365 | OMIM:232300
Mode of Inheritance: Autosomal recessive inheritance (HP:0000007)
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
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
10.00
Palmer RE et al. 2007 Jan (PMID:17056254); Huie ML et al. 1994 Jul (PMID:7981676); Hermans MM et al. 1993 Feb 1 (PMID:8094613); Rohrbach M et al. 2010 Dec (PMID:20882352);
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5
5.50
Pipo JR et al. 2003 Oct (PMID:14643388); Boerkoel CF et al. 1995 Apr (PMID:7717400); Oba-Shinjo SM et al. 2009 Nov (PMID:19588081); Huie ML et al. 1998 Mar 27 (PMID:9535769);
Segregation Evidence Evidence of segregation in one or more families   Sequencing Method 0-3 3
 
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
Aggregate Variant Analysis 0-6
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
1.00
2
Brown BI et al. 1965 Oct 25 (PMID:4286143);
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2 1.00
Reuser AJ et al. 1987 Jun (PMID:3108320); Umapathysivam K et al. 2000 Sep (PMID:10973860); Bali DS et al. 2011 May (PMID:21484825);
Functional Alteration Patient cells 1 0 - 2 2
0.50
1
Reuser AJ et al. 1987 Jun (PMID:3108320);
Non-patient cells 0.5 0 - 1 0.50
Hermans MM et al. 1991 Jul 25 (PMID:1856189);
Models Non-human model organism 2 0 - 4 4 2.00 4
Raben N et al. 1998 Jul 24 (PMID:9668092);
Cell culture model 1 0 - 2
Rescue Rescue in human 2 0 - 4
2.00
Kishnani PS et al. 2006 Jul (PMID:16860134);
Rescue in non-human model organism 2 0 - 4
2.00
Fraites TJ Jr et al. 2002 May (PMID:11991748);
Rescue in cell culture model 1 0 - 2
Rescue in patient cells 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 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
EXPERT CURATION (DATE)
DEFINITIVE
06/09/2017