Deafness-lymphedema-leukemia syndrome: genes and variants

Genes linked to Deafness-lymphedema-leukemia syndrome

• GATA2: Endothelial transcription factor GATA-2

  It maintains hematopoietic stem and progenitor cells and directs development of monocytes, dendritic cells, NK cells, and other blood lineages. Haploinsufficiency causes GATA2 deficiency with immunodeficiency, cytopenias, and high risk of myelodysplastic syndrome or AML.

  35 disease-causing and 596 uncertain variants in GATA2 are linked to Deafness-lymphedema-leukemia syndrome.

Where Deafness-lymphedema-leukemia syndrome variants cluster

• GATA2 GATA-type 2 (positions 349–373): 20 of 35 disease-causing changes, 11.0× more than its size predicts.

Known disease-causing variants in Deafness-lymphedema-leukemia syndrome

Uncertain variants in Deafness-lymphedema-leukemia syndrome that look disease-causing

Which prediction tools work for Deafness-lymphedema-leukemia syndrome

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 100 out of 100
• PolyPhen-2: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Monocytopenia with susceptibility to infections is also caused by GATA2 variants; they fall partly in the same places as the Deafness-lymphedema-leukemia syndrome variants (12 disease-causing).

Diseases related to Deafness-lymphedema-leukemia syndrome

• Acute myeloid leukemia, also linked to GATA2
• GATA2 deficiency with susceptibility to MDS/AML, also linked to GATA2
• Monocytopenia with susceptibility to infections, also linked to GATA2
• Myelodysplastic syndrome, also linked to GATA2

Frequently asked questions

Which genes are linked to Deafness-lymphedema-leukemia syndrome?

In CATVariant, Deafness-lymphedema-leukemia syndrome is linked to 1 analyzed protein: GATA2 (Endothelial transcription factor GATA-2).

How many genetic variants are linked to Deafness-lymphedema-leukemia syndrome?

652 variants: 35 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 596 are of uncertain significance or have conflicting reports.

Which uncertain variants in Deafness-lymphedema-leukemia syndrome look disease-causing?

6 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example GATA2 M388V, GATA2 W360R, GATA2 R361H, GATA2 R362Q and GATA2 P385L. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Deafness-lymphedema-leukemia syndrome?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.99, based on 34 disease-causing and 11 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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