Cytopenias and congenital anaemias
Gene: HBA2
There are two alpha globin genes (HBA1 and HBA2), which are encoded in tandem on chromosome 16. Different Mutations in HBA1/HBA2 are associated with different α-thalassemias and different mode of inheritance: 1) α-thalassemia silent carrier: deletion/mutation that leads to loss of 1 α-globin gene (either HBA1 or HBA2) 2) α-thalassemia trait: deletion/mutations that leads to the loss of 2 α-globin genes either in cis (--/αα) or in trans (-α/-α); 3) Hemoglobin H disease is caused by contiguous gene deletion of HBA1 and HBA2 genes on one chromosome, and a defect (deletional / inactivating small indel /single nucletide variant), in either HBA1 or HBA2 on the other chromosome; 4) 'homozygous alpha-thalassemia' (fatal hydrops fetalis): usually caused by deletions on both chromosomes, leading no/little production of alpha globin and death in utero. The phenotypes relevant to this panel are the α-thalassemia trait and the Hemoglobin H disease. Mostly caused by deletions but rare cases of small indels or point mutations leading to decreased production of the alpha globin chans have been described (16798638, 15481890, 15182057 for example)Created: 11 Mar 2017, 8:56 p.m.
Comment on mode of inheritance: see comment aboveCreated: 10 Mar 2017, 4:30 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Heinz body anemias, 140700; Hemoglobin H disease, nondeletional 613978, alpha thalassemia
Mode of pathogenicity
Other
Comment on mode of inheritance: Monoallelic inheritance reported for Heinz body anemia,140700, no information provided in OMIM for the other phenotypesCreated: 9 Mar 2017, 5:05 p.m.
Comment on list classification: Needs further discussion with clinical teamCreated: 2 Mar 2017, 2:40 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Globin Disorder
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: HBA2 were changed from Globin Disorder; Erythrocytosis; Heinz body anemia,140700; Hemoglobin H disease, nondeletional, 613978; Hypochromic microcytic anemia; Thalassemia, alpha-, 60413 to Erythrocytosis 7, OMIM:617981; Heinz body anemia, OMIM:140700; Hemoglobin H disease, deletional and nondeletional, OMIM:613978; Thalassemia, alpha-, OMIM:604131
Mode of pathogenicity for HBA2 was changed to Other - please provide details in the comments
Promoted to V1 on 11 March 2017, after internal review and discussion with the clinical team.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Mode of inheritance for HBA2 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
Mode of inheritance for HBA2 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for HBA2 were set to Globin Disorder; Erythrocytosis;Heinz body anemia,140700;Hemoglobin H disease, nondeletional, 613978;Hypochromic microcytic anemia;Thalassemia, alpha-, 60413
This gene has been classified as Amber List (Moderate Evidence).
HBA2 was created by LouiseD
HBA2 was added to Cytopaenias and congenital anaemiaspanel. Sources: Radboud University Medical Center, Nijmegen