| Gene/Disease Pair: | NHS : Nance-Horan syndrome |
| MONDO:0010545 | ORPHA:627 | OMIM:302350 | |
| 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 | 16.50 | 10 |
Burdon KP et al. 2003 Nov (PMID:14564667); Sharma S et al. 2008 (PMID:18949062);
|
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| 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 |
6.50
|
3 | ||||||
| Total LOD Score | Canditate Gene Sequencing | Exome/Genome or all genes sequenced in linkage region | ||||||||||
| 2-2.99 | 0.5 | 1 |
Burdon KP et al. 2003 Nov (PMID:14564667);
|
|||||||||
| 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) | 12 |
|
||||||||||
|
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
|
0.5 | ||||||
| Protein Interaction | 0.5 | 0 - 2 | 0.00 | |||||||||
| Expression | 0.5 | 0 - 2 | 0.50 |
Burdon KP et al. 2003 Nov (PMID:14564667);
|
||||||||
| Functional Alteration | Patient cells | 1 | 0 - 2 | 2 |
0.00
|
1 | ||||||
| Non-patient cells | 0.5 | 0 - 1 | 1.00 |
Brooks SP et al. 2010 Jun 15 (PMID:20332100);
|
||||||||
| Models | Non-human model organism | 2 | 0 - 4 | 4 | 1.00 | 2 |
Huang KM et al. 2006 Jan 15 (PMID:16357105);
|
|||||
| 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 |
1.00
|
Brooks SP et al. 2010 Jun 15 (PMID:20332100);
|
||||||||
| 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) | 3.5 |
|
||||||||||
| 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 | 3.5 | 15.5 | YES | ||
| CALCULATED CLASSIFICATION | LIMITED | 1-6 | ||||
| MODERATE | 7-11 | |||||
| STRONG | 12-18 | |||||
| DEFINITIVE | 12-18 AND replication over time | |||||
| Valid contradictory evidence (Y/N)*
|
|
|||||
| CALCULATED CLASSIFICATION (DATE) |
DEFINITIVE
02/12/2018
|
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| EXPERT CURATION (DATE) |
DEFINITIVE
10/20/2017
|
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