Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

AP1S2 : X-Linked Intellectual Disability

MONDO:0060309 | ORPHA:777 | OMIM:300629
Mode of Inheritance: X-linked inheritance (HP:0001427)
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
0.00
Proband with predicted or proven null variant 1.5 0-2 10 5.50 5.5
Tzschach A et al. 2015 Nov (PMID:25649377); Cacciagli P et al. 2014 Mar (PMID:23756445); Borck G et al. 2008 Jul (PMID:18428203); Ballarati L et al. 2012 Feb (PMID:22210230); Saillour Y et al. 2007 Nov (PMID:17617514); Tarpey PS et al. 2006 Dec (PMID:17186471); Carpenter NJ et al. 1999 Jul 30 (PMID:10398241); Turner G et al. 2003 Mar 15 (PMID:12599187);
Proband with other variant type with some evidence of gene impact 0.5 0-1.5 7
0.00
Autosomal Recessive Disease Two variants in trans and at least one de novo or a predicted/proven null variant 2 0-3 12
0.00
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5
0.00
Segregation Evidence Evidence of segregation in one or more families   Sequencing Method 0-3 3
7.00
3  
Total LOD Score Canditate Gene Sequencing Exome/Genome or all genes sequenced in linkage region  
2-2.99 0.5 1
Tarpey PS et al. 2006 Dec (PMID:17186471); Borck G et al. 2008 Jul (PMID:18428203); Saillour Y et al. 2007 Nov (PMID:17617514);
3-4.99 1 2
≥5 1.5 3
Turner G et al. 2003 Mar 15 (PMID:12599187); Pettigrew AL et al. 1991 Feb-Mar (PMID:2018058); Cacciagli P et al. 2014 Mar (PMID:23756445);
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
0.00
Aggregate Variant Analysis 0-6
0.00
Total Genetic Evidence Points (Maximum 12) 8.5
Experimental Evidence
Evidence Category Evidence Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Function Biochemical Function 0.5 0 - 2 2
0.00
1
Protein Interaction 0.5 0 - 2 0.00
Expression 0.5 0 - 2 1.00
Kratzke M et al. 2015 Aug (PMID:25128028);
Functional Alteration Patient cells 1 0 - 2 2
0.00
Non-patient cells 0.5 0 - 1 0.00
Models Non-human model organism 2 0 - 4 4 0.00 2
Cell culture model 1 0 - 2 0.00
Rescue Rescue in human 2 0 - 4
0.00
Rescue in non-human model organism 2 0 - 4
2.00
Glyvuk N et al. 2010 Apr 21 (PMID:20203623); Candiello E et al. 2016 Jul 14 (PMID:27411398);
Rescue in cell culture model 1 0 - 2 0.00
Rescue in patient cells 1 0 - 2 0.00
Total Experimental Evidence Points (Maximum 6) 3

 


 

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 8.5 3 11.5 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
08/16/2017
EXPERT CURATION (DATE)
DEFINITIVE
10/20/2017