Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000507788 | SCV000601222 | pathogenic | not provided | 2021-01-13 | criteria provided, single submitter | clinical testing | This variant causes the premature termination of HBA2 protein synthesis, and has been reported in heterozygous carriers with mild microcytic anemia in the published literature (PMIDs: 16512835 (2006) and 17486494 (2007)). Functional studies showed that this variant does not affect RNA splicing, but the mRNA transcript is subject to nonsense-mediated decay (PMID: 16512835 (2006)). Therefore, the variant is classified as pathogenic. |
ARUP Laboratories, |
RCV000507788 | SCV002048279 | pathogenic | not provided | 2022-08-23 | criteria provided, single submitter | clinical testing | The HBA2 c.69delC; p.Glu24SerfsTer26 variant (rs1270810159), also known as codon 22 (-C), is reported in the literature in the heterozygous state in individuals with microcytic and hypochromic anemia (Luo 2007, Pereira 2006). This variant is also reported in ClinVar (Variation ID: 439123). This variant is found in the general population with an overall allele frequency of 0.006% (3/53510 alleles) in the Genome Aggregation Database. This variant causes a frameshift by deleting a single nucleotide, and has been shown to result in a truncated mRNA subject to nonsense-mediated decay (Pereira 2006). Based on available information, this variant is considered to be pathogenic. References: Luo HY et al. Two new alpha-thalassemia frameshift mutations. Hemoglobin. 2007;31(2):135-9. PMID: 17486494. Pereira FJ et al. Human alpha2-globin nonsense-mediated mRNA decay induced by a novel alpha-thalassaemia frameshift mutation at codon 22. Br J Haematol. 2006 Apr;133(1):98-102. PMID: 16512835. |
Natera, |
RCV001027962 | SCV001190709 | pathogenic | alpha Thalassemia | 2019-05-20 | no assertion criteria provided | clinical testing |