Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001812924 | SCV001472463 | uncertain significance | not provided | 2019-11-25 | criteria provided, single submitter | clinical testing | The HBB c.*74A>G variant (rs369101035) is reported in the literature in individuals affected with beta-thalassemia or mild anemia, although its clinical significance was not determined in these studies (Al-Gazali 2010, Daniel 2014). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant occurs in the 3' untranslated region at a nucleotide that is moderately conserved and is located upstream of the poly(A) signal. However, given the lack of clinical and functional data, the significance of the c.*74A>G variant is uncertain at this time. References: Al-Gazali L and Ali BR. Mutations of a country: a mutation review of single gene disorders in the United Arab Emirates (UAE). Hum Mutat. 2010 May;31(5):505-20. Daniel Y et al. Evaluation of the validity of Hb A2 and mean corpuscular haemoglobin action values in antenatal screening for beta thalassaemia carriers in England. Br J Haematol. 2014 Aug;166(4):607-11. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001293509 | SCV001482096 | uncertain significance | not specified | 2024-08-29 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.*74A>G is located in the untranslated mRNA region downstream of the termination codon, not affecting the 'known' polyA tail signal. The variant was absent in 251040 control chromosomes (gnomAD v2). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.*74A>G has been reported in the literature in individuals not meeting the established criteria for beta thalassaemia carrier status based on cutoff values for MCH (<27pg) and HbA2 levels (>/=4.0%) (Daniel_2014). These report(s) do not provide unequivocal conclusions about association of the variant with Hemoglobinopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 20437613, 24754789). ClinVar contains an entry for this variant (Variation ID: 993837). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001812924 | SCV004219846 | likely benign | not provided | 2022-09-16 | criteria provided, single submitter | clinical testing |