IthaID: 2487

Names and Sequences

Functionality:	Globin gene causative mutation	Pathogenicity:	Pathogenic / Likely Pathogenic
Common Name:	CD 31 AGG>GGG [Arg>Gly]	HGVS Name:	HBA2:c.94A>G
Hb Name:	Hb Maranon	Protein Info:	α2 31(B12) Arg>Gly
Also known as:

We follow the HGVS sequence variant nomenclature and IUPAC standards.

Comments: This mutation causes the activation of a cryptic splice site located 49 bp upstream of the exon1-intron1 boundary in both HBA2 long and short isoforms, thus generating a frameshift and a premature termination codon between codons 48 and 49 in the second exon. In Hb Maranon, instability is due to the substituted Arg residue at position 12 of the B helix of the alpha2-globin chain that seems to alter the hydrophobic environment required for the distal heme binding, causing an alpha-thalassemia phenotype.

External Links

HbVar

Phenotype

Hemoglobinopathy Group:	Thalassaemia and Structural Haemoglobinopathy
Hemoglobinopathy Subgroup:	α-thalassaemia, α-chain variant
Allele Phenotype:	α⁺
Stability:	Hyperunstable
Oxygen Affinity:	N/A
Associated Phenotypes:	N/A

IthaPhen

Heterozygous records (preview in IthaPhen)

Location

Chromosome:	16
Locus:	NG_000006.1
Locus Location:	33869
Size:	1 bp
Located at:	α2
Specific Location:	Exon 1

Other details

Type of Mutation:	Point-Mutation(Substitution)
Effect on Gene/Protein Function:	Cryptic splice site (mRNA Processing), Missense codons (Protein Structure)
Ethnic Origin:	Indian
Molecular mechanism:	Altered α1β1 interface
Inheritance:	Recessive
DNA Sequence Determined:	Yes

In silico pathogenicity prediction

Publications / Origin

Qadah T, Finlayson J, Joly P, Ghassemifar R, Molecular and cellular analysis of a novel HBA2 mutation (HBA2: c.94A > G) shows activation of a cryptic splice site and generation of a premature termination codon., Hemoglobin , 38(1), 13-8, 2014
de la Fuente-Gonzalo F, Nieto JM, Ricard P, Anguita J, Martínez R, Cervera A, Villegas A, González FA, Ropero P, Hb Cervantes, Hb Marañón, Hb La Mancha and Hb Goya: Description of 4 new haemoglobinopathies., Clin. Biochem. , 48(10), 662-7, 2015

Created on 2014-06-04 16:23:14, Last reviewed on 2017-05-30 09:56:13 (Show full history)

A/A	Date	Curator(s)	Comments
1	2014-06-04 16:23:14	The IthaGenes Curation Team	Created
2	2016-08-23 10:09:57	The IthaGenes Curation Team	Reviewed. Update of mutation comment section. Update of protein information, including addition of variant name. Structural Hb variant field checked and phenotype information added.
3	2016-08-24 14:08:07	The IthaGenes Curation Team	Reviewed.
4	2016-09-09 11:50:31	The IthaGenes Curation Team	Reviewed. Reference added.
5	2017-05-08 11:35:22	The IthaGenes Curation Team	Reviewed. Protein info added.
6	2017-05-30 09:56:13	The IthaGenes Curation Team	Reviewed. Protein info section updated.

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