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Gene-disease assertions not curated here (add link or write note):

Disease

Spinocerebellar ataxia type 10

Inheritance

Autosomal dominant

Prevalence

 Unknown

Source: ORPHA:98761

Rapid or full curation?

  • Rapid
  • Full

ClinGen / GenCC / BabySeq / HGMD / OMIM

ClinGen - none; GenCC - Ophanet (supportive); Babyseq - none; HGMD - 3 repeat variation variants listed with association to spinocerebellar ataxia 10.

Clinical Validity Scoring Notes and points

11017075 - A pentanucleotide expansion of ATTCT in intron 9 of the ATXN10 (aka SCA10) was identified in a large Mexican family with spinocerebellar ataxia. Affected individuals had repeats in the range of 800 to >3000A control cohort of 562 control chromosomes showed range of 10-22 repeats. Fig 1 shows PCR analysis performed in 4 families, counting 12 segregations here. Earlier age of onset observed in individuals with larger expansions (fig 4). Since repeat sizes are different in all 4 families, counting 0.5x4= 2 VARIANT POINTS, 12 SEGREGATIONS

24278426 - An individual with Sioux Native American ancestry and features of spinocerebellar ataxia with an expanded allele of 1400. Age of onset 83 and authors suggest reduced penetrance. 0.5 VARIANT POINTS

28542277 - Japanese family with SCA type 10. Proband and her mother were genotyped and found to have an expanded allele. 0.5 VARIANT POINTS, 1 SEGREGATION.

36092952 - Pure (ATTCT)n and mixed (ATTCT)n-(ATTCC)n expansions reported in the same Mexican family. Found considerable mosaicism of the repeat expansion. Individuals with the mixed expansion showed signs of SCA, but of the 6 individuals with the pure expansion, 5 were unaffected and 1 presented with Parkinson disease at age 38. Two were passed the age of onset expected in this family by over 20 years. They propose that the pure ATTCTn expansion is non-pathogenic or has low penetrance with mild disease course.

36199580

26295943 - SMRT sequencing performed in three patients with known expansions in ATXN10.

Not scored: 23117922 - Expansion in ATXN10 observed in individual who also had SCA2 expansion, dual dx, did not score. 23083689 - dual dx of Huntington disease and SCA10

Source:

Clinical Validity Points Total

Source:

Clinical Validity Classification

 Classifications (pts)

Definitive (12pts)

Strong (12pts)

Moderate (7-11pts)

Limited (0.1-6pts)

No genetic evidence

Refuted

Disputed

Source:

Molecular Mechanism

 Mechanisms

Loss of function

Gain of function

Dominant negative

Unknown

Other

Loss of function / Gain of function / Dominant Negative

Reduced penetrance papers:

  • 16717236 - A Brazilian family in which the affected proband had 400-repeat expansion, two unaffected sibs and her unaffected father had repeats f 370 and 360.

15127363 - expanded alleles highly unstable when paternally transmitted

Penetrance

 options

Complete (100%)

High (≥80%)

Moderate  (<80% and >20%)

Low (≤20%)

(list source/PMID)

Source:

Age of Onset

 options

Congenital

Pediatric

Adolescent

Adulthood

Late adulthood

(list source/PMID)

Severity

 Options

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

 Examples

- 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

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