ClinVar Miner

Submissions for variant NM_000517.4(HBA2):c.142G>C (p.Asp48His) (rs281864834)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757355 SCV000885546 likely pathogenic not provided 2018-01-09 criteria provided, single submitter clinical testing The Hb Hasharon variant (HBA2: c.142G>C, Asp47His) (rs281864834), also known as Hb Sealy and Hb L-Ferrara, has been observed in multiple families of Jewish, Italian and Middle Eastern descent (Charache 1969, Kimura 2015, Nagel 1969, Pich 1978, Schneider 1968). Although it has not been associated with alpha-thalassemia, individuals heterozygous for this variant have lower levels of the Hb Hasharon alpha chain than expected (Schneider 1968, Charache 1969), and some have been reported to have microcytosis and hypochromia (Kimura 2015). Functional characterization of Hb Hasharon indicates that the variant alpha chain has reduced stability in vitro (Charache 1969) and in vivo (Molchanova 1994). The variant is listed in the ClinVar (Variation ID: 15636), and observed in the Genome Aggregation Database general population database at a frequency of 0.009 percent (11/122360 alleles). The aspartate at residue 47 is moderately conserved, and computation algorithms (Mutation Taster, PolyPhen-2, SIFT) predict that the variant has an impact on the protein. Based on the above information, the variant is classified as likely pathogenic. REFERENCES Link to HbVar database for Hb Hasharon: Charache S et al. Hemoglobin Hasharon (alpha-2-47 his(CD5)beta-2): a hemoglobin found in low concentration. J Clin Invest. 1969; 48(5):834-47. Kimura E et al. Investigating alpha-globin structural variants: a retrospective review of 135,000 Brazilian individuals. Rev Bras Hematol Hemoter. 2015; 37(2):103-8. Molchanova T et al. The differences in quantities of alpha 2- and alpha 1-globin gene variants in heterozygotes. Br J Haematol. 1994; 88(2):300-6. Nagel R et al. Hemoglobin L Ferrara in a Jewish family associated with a hemolytic state in the propositus. Blood. 1969; 34(2):157-65. Pich P et al. Interaction between Hb Hasharon and alpha-thalassemia: an approach to the problem of the number of human alpha loci. Blood. 1978; 51(2):339-46. Schneider R et al. Hemoglobin sealy (alpha 2-47His-beta 2): a new variant in a Jewish family. Am J Hum Genet. 1968; 20(2):151-6.
OMIM RCV000016910 SCV000037181 other HEMOGLOBIN L (FERRARA) 2018-05-21 no assertion criteria provided literature only
OMIM RCV000016911 SCV000037182 other HEMOGLOBIN HASHARON 2018-05-21 no assertion criteria provided literature only
OMIM RCV000016912 SCV000037183 other HEMOGLOBIN SINAI 2018-05-21 no assertion criteria provided literature only
OMIM RCV000016913 SCV000037184 other HEMOGLOBIN SEALY 2018-05-21 no assertion criteria provided literature only

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