Inheritance

Autosomal dominant

Prevalence

 MDS in general is about 4.4 to 4.6 cases per 100,000 people

Source: Myelodysplastic Syndromes Treatment (PDQ®)

Rapid or full curation?

ClinGen / GenCC / BabySeq / HGMD / OMIM

Clinical Validity Scoring Notes and points

Variant/Case Evidence:

PMID 32641076 c.1A > G variant found in one individual with unexplained hemolysis by WES. This could potentially be on the spectrum of myeloproliferative disorder (1 pt)

PMID 31173385 c.1198G>A, p.E400K variant found in an individual with features of MDS/MPN-overlap syndrome. Variant present in gnomAD v4 AF=0.18% (European chromosomes) so no points given.

PMID 31102422 c.1261C>T p.Arg421Trp variant identified in individual with ALL (no points for inconsistent phenotype)

PMID 24092923 Consanguineous family with c.671insGGCCCCG p. Asp231Glyfs*38 with autoimmune disorders and acute lymphoblastic leukemia (ALL). Does not match cell lineage or inheritance patterns (no points)

Open

PMID 26457647- Cohort of JMML, multiple somatic in SH2B3. One germline variant p.E400K. No points due to high frequency

Segregation Evidence:

Case/Control Evidence:

Experimental Evidence:

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