Inheritance

X-linked

Prevalence

 Overall incidence of Diamond-Blackfan 5-7 per million

Source: https://medlineplus.gov/genetics/condition/diamond-blackfan-anemia/

Rapid or full curation?

ClinGen / GenCC / BabySeq / HGMD / OMIM

Not in ClinGen (In Scope for General GCEP and CAYA GCEP)

GenCC- XL Diamond-Blackfan anemia 14 with mandibulofacial dysostosis (Limited- Invitae)

OMIM- ?Diamond-Blackfan anemia 14 with mandibulofacial dysostosis XL

Clinical Validity Scoring Notes and points

Variant/Case Evidence:

PMID 24942156- Variant (c.191A>G p.Glu64Gly) in one male with features of Diamond-Blackfan anemia and facial features suggestive of Treacher Collins. This variant was also found in an male cousin with facial features but no overt features of Diamond-Blackfan but was reported to have “elevated mean corpuscular volume, eADA and hemoglobin F were consistent with DBA markers” by age 16. This segregation is through three unaffected females. Family previously described in PMID: 11424144 (0.5 pts)

PMID 30503522- The same c.191A>G p.Glu64Gly was identified in two related individuals with DBA through WES (0.5 pts)

Segregation Evidence:

Case/Control Evidence:

Experimental Evidence:

PMID 30201955- Functional study in yeast cells with the E64G variant noted above showed impact to protein function (1 pt)

PMID 29551269- Functional studies show impact mutations in TRS2; some studies seem to be a repeat of above.

Source:

Clinical Validity Points Total

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