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RPS27 Gene Curation

RPS27 Gene Curation

Owned by Katherine Lafferty
2025-01-17
2 min read

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

Disease

Diamond-Blackfan anemia 17

Disease

Diamond-Blackfan anemia 17

Inheritance

Autosomal dominant

Prevalence

Orphanet

Medline Plus Genetics

Overall incidence of Diamond-Blackfan 5-7 per million

Source: Diamond-Blackfan anemia: MedlinePlus Genetics

Rapid or full curation?

Rapid
Full

ClinGen / GenCC / BabySeq / HGMD / OMIM

Not in ClinGen (In Scope for Prenatal and CAYA GCEPs)

GenCC- AD Diamond-Blackfan anemia 17 (Limited- PanelApp Australia and Invitae)

OMIM- AD ?Diamond-Blackfan anemia 17

Clinical Validity Scoring Notes and points

Variant/Case Evidence:

PMID 25424902- c.89delC, p.Tyr31Thrfs*5 variant found de novo and an individual characteristics of DBA (2.5 pts)

Segregation Evidence:

Case/Control Evidence:

Experimental Evidence:

PMID 25424902- Knockdown of RPS27 on erythroid lineage cells showed defective pre-ribosomal RNA processing (1 pt). Zebrafish models of rps27 mutations showed impairments of erythrocyte production and tail and/or brain development. (2 pts)

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

Limited

Source:

Molecular Mechanism

Loss of function

Gain of function

Dominant negative

Unknown

Other

Loss of function / Gain of function / Dominant Negative

 

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

 

 

 

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