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Disease

Inheritance

Autosomal recessive

Prevalence

Expand
titlePossible sources

Orphanet

Medline Plus Genetics

 N/A

Rapid or full curation?

  •  Rapid
  •  Full

ClinGen / GenCC / BabySeq / HGMD

ClinGen - Dosage sensitivity curation: No evidence for triplosensitivity or haploinsufficiency. Tandem duplications that include LBX1, BTRC, and POLL, and had a breakpoint within FBXW4 (DAC) reported in individuals with split hand-foot malformation.

GENCC - no curations

HGMD - DM? Variants listed with several reported phenotypes (schizophrenia, head and neck squamous cell carcinoma, developmental disorder, congenital heart disease, prostate cancer). 1 DM duplication associated with autism. Did not review variants further.

Clinical Validity Scoring Notes and points

 N/A

Clinical Validity Points Total

 N/A

Clinical Validity Classification

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titleClassifications (pts)

Definitive (12pts)

Strong (12pts)

Moderate (7-11pts)

Limited (0.1-6pts)

No genetic evidence

Refuted

Disputed

Limited/No Genetic Evidence

Molecular Mechanism

Expand
titleMechanisms

Loss of function

Gain of function

Dominant negative

Unknown

Other

Loss of function / Gain of function / Dominant Negative

Penetrance

Expand
titleoptions

Complete (100%)

High (≥90%)

Reduced  (<90% and >10%)

Low (≤10%)

(list source/PMID)

 N/A

Age of Onset

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titleoptions

Congenital

Pediatric

Adolescent

Adulthood

Late adulthood

(list source/PMID)

 N/A

Severity

Expand
titleOptions

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.

 N/A

Clinical Features

 N/A

Gene SOPs & Notes

 N/A

Curation Summary:

Expand
titleExamples

- 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-dsiease relationship is limited

 N/A

Case ID, Curator name, Date, Jira ticket link

Andrea Oza, 06/14/2023

Jira Legacy
serverSystem JIRA
serverIdeee25142-2510-336f-918a-865682ebdf2e
keyCIT-127

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