Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 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: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=65 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 |