Gene Validity Classification Summary

Gene/Disease Pair:

HPRT1 : Lesch-Nyhan Syndrome

MONDO:0010298 | ORPHA:510 | OMIM:300322
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
4.50
4.5
Gibbs RA et al. 1989 Mar (PMID:2928313); Aral B et al. 1996 (PMID:8664901);
Proband with predicted or proven null variant 1.5 0-2 10 4.50 4.5
Gibbs RA et al. 1989 Mar (PMID:2928313); Fujimori S et al. 1990 Apr (PMID:2323782);
Proband with other variant type with some evidence of gene impact 0.5 0-1.5 7
0.50
0.5
Gibbs RA et al. 1989 Mar (PMID:2928313);
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
0.00
 
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
0.00
Aggregate Variant Analysis 0-6
0.00
Total Genetic Evidence Points (Maximum 12) 9.5
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
Thul PJ et al. 2017 May 26 (PMID:28495876);
Functional Alteration Patient cells 1 0 - 2 2
0.00
1
Non-patient cells 0.5 0 - 1 1.00
Frank S et al. 2013 Nov 9 (PMID:24206569);
Models Non-human model organism 2 0 - 4 4 1.00 1
Kuehn MR et al. 1987 Mar 19-25 (PMID:3029599);
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
0.00
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 9.5 3 12.5 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
03/08/2018
EXPERT CURATION (DATE)
DEFINITIVE
03/07/2018