Clinical Domain Working Groups

Hemoglobinopathy Variant Curation Expert Panel

Membership

The Hemoglobinopathy VCEP is a joint effort of the ITHANET portal for hemoglobinopathies and the Global Globin Network by the Human Variome Project. This VCEP will focus on the review and annotation of variants that are related to hemoglobinopathies, the most common monogenic diseases in the world. They are caused by variants in the globin gene clusters, namely α-globin locus (NG_000006) which includes genes HBA1, HBA2 and HBZ and β-globin locus (NG_000007) which includes genes HBB, HBD, HBG1, HBG2 and HBE and the regulatory element LCRB. Although different disease/phenotype ontologies, such as HPO, Orphanet and ICD, provide different classifications, hemoglobinopathies can be broadly divided into the following conditions:

  1. Thalassaemias, which can be further divided into the following conditions:
    1. α-thalassaemia
    2. β-thalassaemia
    3. δ-thalassaemia
    4. δβ-thalassaemia
    5. εγδβ-thalassaemia and γδβ-thalassaemia
  2. Sickle-cell disorders
  3. Other hemoglobinopathies, which include Hemoglobin E disease, Hemoglobin C disease and Hemoglobin D disease, amongst other rarer structural hemoglobinopathies and hemoglobinopathies that result from compound heterozygosity of structural variants with thalassaemia or sickle-cell disease
  4. Hereditary persistence of fetal hemoglobin (HPFH)

 

The VCEP will begin the variant annotation with the genes located in the globin gene clusters, which carry the most common and highly penetrant variants. Full lists of genes and variants are available on the ITHANET portal, as follows:

    1. Genes: http://www.ithanet.eu/db/ithagenes?action=glist
    2. Variants: http://www.ithanet.eu/db/ithagenes?action=list

 

The VCEP will prioritize the review of variants that are currently submitted in ClinVar, particularly those with conflicting interpretations. In addition and to enable broader benefit to the community, the Panel will make an early submission of all variants stored in the IthaGenes database, before completing the review of all the variants.

Expert Panel Status

Step 1
Step 2
Step 3
Step 4
Define Group
Completed Dec. 2019
Develop Classification Rules
Pilot Rules
Expert Panel Approval

Expert Panel Membership

Membership spans many fields, including genetics, medical, academia, and industry.


Chairs

Coordinators
Please contact a coordinator if you have questions.