Inheritance

Autosomal dominant

Prevalence

 5 to 7 per million

Source: Medline Plus Genetics

Rapid or full curation?

ClinGen / GenCC / BabySeq / HGMD / OMIM

No ClinGen classification

Classified as limited by Ambry (8/31/2018) and Invitae (3/15/2019)

Classified as supportive by Orphanet (9/14/2021)

Classified as moderate by PanelApp Australia (3/6/2021)

Clinical Validity Scoring Notes and points

Variant/Case Evidence:

PMID: 28280134

• Identified p.L51S variant in a father and son with Diamond-Blackfan anemia using WES

• Variant is absent from gnomAD

• Pre-rRNA processing evaluation in mononuclear cells from the proband showed an increase in the 36S pre-rRNA compared to wt RPL18 consistent with the known effects of a subset of large subunit RP defect on pre-rRNA processing

• 0.1 + 0.5 (functional data) = 0.6 pts

PMID: 30503522

• Identified p.L51S variant in an affected proband using WES

• Same variant as above

• 0.1 pt

Segregation Evidence:

Case/Control Evidence:

Experimental Evidence:

PMID: 32075953

• Generated a RPL18 mutant line in zebrafish

• Molecular characterization of this mutant line demonstrated that RPL18 deficiency mirrored the erythroid defects of Diamond-Blackfan anemia through a lack of mature red blood cells - 2 pts

Source:

Clinical Validity Points Total

2.7

Source:

Clinical Validity Classification

Limited

Source:

Molecular Mechanism

Loss of function / Gain of function / Dominant Negative

Penetrance

(list source/PMID)

Source:

Age of Onset

(list source/PMID)

Severity

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

Case ID, Curator name, Date, Jira ticket link