Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000757366 | SCV000885560 | uncertain significance | not provided | 2018-06-28 | criteria provided, single submitter | clinical testing | The Hb Akron c.158A>T; Asp52Val variant (rs33919924) has been described in the heterozygous state in an individual with normal clinical presentation in the HbVar database (see link). However, its phenotype when found with other globin variants is unknown. This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. Additionally, one other variant at this codon (c.157G>A, Asp52Asn) has been reported in trans with other hemoglobin variants (Hb C, Hb S) without any clinically significant phenotype (HbVar, Boucher 2016, Cook 2013, Konotey-Ahulu 1971), and is considered benign. The aspartic acid at codon 52 is weakly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the Asp52Val variant is uncertain at this time. References: Link to HbVar Database: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=338&.cgifields=histD Boucher MO et al Mild Microcytic Anemia in an Infant with a Compound Heterozygosity for Hb C (HBB: c.19G?>?A) and Hb Osu Christiansborg (HBB: c.157G?>?A). Hemoglobin. 2016 40(3):208-9. Cook CM et al. The clinical and laboratory spectrum of Hb C (Beta6(A3)Glu>Lys, GAG>AAG) disease. Hemoglobin. 2013 37(1):16-25. Konotey-Ahulu FI et al. Haemoglobin Osu-Christiansborg: a new beta-chain variant of haemoglobin A ( beta52 (D3) aspartic acid leads to asparagine) in combination with haemoglobin S. J Med Genet. 1971 8(3):302-5. |