Inheritance

Autosomal dominant

Prevalence

  5 to 7 per million

Source: Medline Plus Genetics

Rapid or full curation?

ClinGen / GenCC / BabySeq / HGMD / OMIM

No published ClinGen curation

2 limited classifications in GenCC - PanelApp Australia (3/6/2021) and Invitae (3/25/2019)

Clinical Validity Scoring Notes and points

Variant/Case Evidence:

PMID: 25424902

• Identified a de novo splicing error variant (c.-2-1G>A) in patient with Diamond-Blackfan anemia

• Zebrafish model of the variant showed impairments of erythrocyte production and tail and/or brain development

• 0.1 pts + 0.5 (functional data) + 0.5 (de novo) = 1.1 pts

PMID: 37897121

• 26 yo F proband with Diamond-Blackfan anemia had digenic interaction between non-allelic RPS19 and RPL27 variants (c.-3+1G>C) - confirmed with a machine learning structural model, co-segregation analysis, and RNA sequencing

• 0.1 pts

PMID: 38988374

• Identified de novo variant (c.-2-1 G> A) in 10 month old F with Diamond-Blackfan anemia through WES

• 0.1 pts

https://doi.org/10.1182/blood-2019-121710

• Identified a 464 bp deletion in the 3rd intron of RPL27 through WES in a patient with Diamond-Blackfan anemia

• Concluded that this deletion causes aberrant splicing leading to an unstable RPL27 mRNA

• 0.5 pts

Segregation Evidence:

Case/Control Evidence:

Experimental Evidence:

Source:

Clinical Validity Points Total

1.8

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