ClinVar Miner

Submissions for variant NM_000517.6(HBA2):c.2del (p.Met1fs)

dbSNP: rs63750678
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985719 SCV001134192 pathogenic not provided 2019-05-29 criteria provided, single submitter clinical testing This variant is located in the translation initiation codon of the HBA2 mRNA and is predicted to interfere with HBA2 protein synthesis. It has been reported in an individual with Hb H disease in the published literature (PMID: 9322079 (1997)).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000985719 SCV001474443 pathogenic not provided 2021-03-26 criteria provided, single submitter clinical testing The HBA2 c.2delT; p.Met1? variant (rs63750678), also known as initiation codon (-T), is reported in the literature in individuals affected with HbH disease who also carried a large deletion encompassing both the HBA1 and HBA2 genes on the other chromosome (see link to HbVar and references therein; Viprakasit 2005). This variant is reported in ClinVar (Variation ID: 15692), and abolishes the canonical initiation codon of HBA2, so it is predicted to result in an absent protein. Other variants that disrupt the initiation codon have been reported in individuals with alpha thalassemias and are considered pathogenic (Eng 2006, Olivieri 1987). Based on available information, the c.2delT; p.Met1? variant is considered to be pathogenic. References: Link to HbVar for Initiation codon (-T): http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=1062&.cgifields=histD Eng B et al. Three new alpha-thalassemia point mutations ascertained through newborn screening. Hemoglobin. 2006;30(2):149-53. Olivieri NF et al. An alpha-globin gene initiation codon mutation in a black family with HbH disease. Blood. 1987 Sep;70(3):729-32. Viprakasit V et al. A rare association of alphaO-thalassemia (--SEA) and an initiation codon mutation (ATG-->A-G) of the alpha2 gene causes Hb H disease in Thailand. Hemoglobin. 2005;29(3):235-40.
OMIM RCV000016983 SCV000037255 pathogenic Hemoglobin H disease, nondeletional 2005-01-01 no assertion criteria provided literature only
Natera, Inc. RCV001831577 SCV002093836 pathogenic alpha Thalassemia 2018-08-31 no assertion criteria provided clinical testing

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