Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985726 | SCV001134199 | pathogenic | not provided | 2019-06-25 | criteria provided, single submitter | clinical testing | The variant disrupts the natural stop codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data. |
| Invitae | RCV000985726 | SCV002245966 | pathogenic | not provided | 2023-09-26 | criteria provided, single submitter | clinical testing | This sequence change disrupts the translational stop signal of the HBA2 mRNA. It is expected to extend the length of the HBA2 protein by 31 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This protein extension has been observed in individual(s) with hemoglobin H disease (PMID: 2372512, 8602995, 21637442). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as Hb Icaria in literature. ClinVar contains an entry for this variant (Variation ID: 15626). This variant results in an extension of the HBA2 protein. Other variant(s) that result in a similarly extended protein product (p.*143Glnext*31) have been determined to be pathogenic (PMID: 2298455, 4944483, 12393486, 20507641). This suggests that these extensions are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| 3billion | RCV002250461 | SCV002521042 | uncertain significance | alpha Thalassemia | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Stop-lost: predicted to change the length of the protein and disrupt normal protein function. The variant has been reported to be associated with HBA2 related disorder (ClinVar ID: VCV000015626 / PMID: 21637442, 2372512, 8602995). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| OMIM | RCV000016893 | SCV000037164 | other | HEMOGLOBIN ICARIA | 2018-05-21 | no assertion criteria provided | literature only | |
| OMIM | RCV000022603 | SCV000043892 | pathogenic | Hemoglobin H disease, nondeletional | 1996-02-01 | no assertion criteria provided | literature only |