Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

HSD17B10 : HSD10 disease

HGNC:4800 | MONDO_0010327
Mode of Inheritance: X-linked inheritance (HP:0001417)
Expert Panel: Fatty Acid Oxidation Disorders EP
SOP: Gene Clinical Validity Standard Operating Procedures (SOP), Version 6

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 2
4
4
Oerum S et al. 2017 Dec (PMID:28888424); García-Villoria J et al. 2009 Jan (PMID:18996107);
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 11
5.2
5.2
Oerum S et al. 2017 Dec (PMID:28888424); Ofman R et al. 2003 May (PMID:12696021); Seaver LH et al. 2011 Nov 22 (PMID:22132097); Yang SY et al. 2009 Sep 1 (PMID:19706438); García-Villoria J et al. 2009 Jan (PMID:18996107); Rauschenberger K et al. 2010 Feb (PMID:20077426);
Autosomal Recessive Disease Two variants in trans and at least one de novo or a predicted/proven null variant 2 0-3 12
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5
Segregation Evidence   Summed LOD Family Count  
Candidate gene sequencing
Exome/genome or all genes sequenced in linkage region
Total Summed LOD Score    
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) 9.2
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
0.5
1
Yang SY et al. 2005 Oct (PMID:16176262);
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2 1 0.5
He XY et al. 2001 Sep (PMID:11559359);
Functional Alteration Patient cells 1 0 - 2 2 1
1
2
Rauschenberger K et al. 2010 Feb (PMID:20077426);
Non-patient cells 0.5 0 - 1 1 1
Deutschmann AJ et al. 2014 Jul 1 (PMID:24549042);
Models Non-human model organism 2 0 - 4 4 1 1 1
Rauschenberger K et al. 2010 Feb (PMID:20077426);
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) 4

 


 

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 9.2 4 13.2 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
10/04/2018
EXPERT CURATION (DATE)
Definitive
10/09/2018