/
IN PROGRESS TBP Gene Curation

IN PROGRESS TBP Gene Curation

Owned by Andrea Oza
2024-07-11
2 min read

Gene-disease assertions not curated here (add link or write note): Curated normal max repeat ONLY for ExpansionHunter validation.

Disease

Spinocerebellar ataxia type 17

Disease

Spinocerebellar ataxia type 17

Inheritance

Autosomal dominant

Prevalence

Orphanet

Medline Plus Genetics

 

Source:

Rapid or full curation?

Rapid
Full

ClinGen / GenCC / BabySeq / HGMD / OMIM

 

Clinical Validity Scoring Notes and points

Variant/Case Evidence:

Segregation Evidence:

Case/Control Evidence:

Experimental Evidence:

Source:

Clinical Validity Points Total

 

Source:

Clinical Validity Classification

Definitive (12pts)

Strong (12pts)

Moderate (7-11pts)

Limited (0.1-6pts)

No genetic evidence

Refuted

Disputed

 

Source:

Molecular Mechanism

Loss of function

Gain of function

Dominant negative

Unknown

Other

Loss of function / Gain of function / Dominant Negative

 

Tandem repeat expansion - CAG/CAA (polyglutamine) in the coding region of exon 3. CAA interruptions are normally present in primarily CAG repeat.

  • In the interest of time for the ExpansionHunter validation, I am setting the normal max at 40 based on the resources below. I only need this value for specificity, so we can adjust for reporting purposes in the future.

 

Review:

  • Stripy: Normal - 25-42, pathogenic ≥43

  • Gnomad: Normal ≤ 42, Pathogenic ≥ 43

  • STRchive: Normal max 40, pathogenic min 49

  • GeneReviews - normal 25-40, reduced penetrance 41-48, full penetrance >48

  •  

Penetrance

Complete (100%)

High (≥80%)

Moderate  (<80% and >20%)

Low (≤20%)

(list source/PMID)

 

Source:

Age of Onset

Congenital

Pediatric

Adolescent

Adulthood

Late adulthood

(list source/PMID)

 

Severity

Embryonic lethal - presence of a pathogenic variant or variants is not compatible with life. The penetrance must be complete.
Severe - presence of a pathogenic variant or variant(s) results in significantly reduced fitness. The penetrance must be complete or high.
Moderate - significant morbidity or mortality due to clinical features, but fitness may not be reduced, or penetrance is reduced.
Mild - Presence of a variant or variant(s) is not associated with reduced fitness, no significant morbidity or mortality, and/or penetrance is low.
None - presence of a variant results in no phenotype. An example is recessive disorders in which no phenotype is reported in carriers.

 

Clinical Features

 

Sources:

HPO Terms

https://hpo.jax.org/app/

 

Gene SOPs & Notes

 LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant

Curation Summary

- The @GENE@ is associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Variable expression or severity:
The severity and expressivity of the disorder is highly variable, even within families.
- If multiple conditions associated with the gene:
It has also been associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Limited evidence gene: The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dIsease relationship is limited

 

Case ID, Curator name, Date, Jira ticket link

 

 

 

Related content