Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

C1QB : Immunodeficiency due to an early component of complement deficiency

HGNC:1242 | OrphaNet: ORPHA169147 | OMIM:613652
Mode of Inheritance: Autosomal recessive inheritance (HP:0000007)

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 8.0 10
Petry F et al. 1997 Dec (PMID:9476130); Marquart HV et al. 2007 Jul (PMID:17513176); McAdam RA et al. 1988 (PMID:2894352); Troedson C et al. 2013 May (PMID:23651859); Higuchi Y et al. 2013 Oct 28 (PMID:24160257); van Schaarenburg RA et al. 2015 Mar (PMID:25454803);
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5 2.0
Segregation Evidence Evidence of segregation in one or more families LOD Score Examples 3 5 0-7 7 3.5 3.5
Marquart HV et al. 2007 Jul (PMID:17513176); Higuchi Y et al. 2013 Oct 28 (PMID:24160257);
2 4
1.5 3
1 1.5
   
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 12
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 1.0 1
van Schaarenburg RA et al. 2015 Mar (PMID:25454803); Higuchi Y et al. 2013 Oct 28 (PMID:24160257); McAdam RA et al. 1988 (PMID:2894352); Petry F et al. 1997 Dec (PMID:9476130); Marquart HV et al. 2007 Jul (PMID:17513176); van Schaarenburg RA et al. 2015 Mar (PMID:25454803);
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2
Functional Alteration Patient cells 1 0 - 2 2 2.0 2
McAdam RA et al. 1988 (PMID:2894352);
Non-patient cells 0.5 0 - 1
Models & Rescue Animal model 2 0 - 4 4 2.0 2
Miura-Shimura Y et al. 2002 Aug 1 (PMID:12133956);
Cell culture model system 1 0 - 2
Rescue in animal model 2 0 - 4
Rescue in engineered equivalent 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 12 5 17 YES
CALCULATED CLASSIFICATION LIMITED 1-6
MODERATE 7-11
STRONG 12-18
DEFINITIVE 12-18 AND replication over time
Valid contradictory evidence (Y/N)*
CALCULATED CLASSIFICATION (DATE)
DEFINITIVE
06/13/2016
EXPERT CURATION (DATE)
DEFINITIVE
01/09/2017