Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001811154 | SCV000885554 | likely benign | not provided | 2023-12-06 | criteria provided, single submitter | clinical testing | The Hb J-Bangkok variant (HBB: c.170G>A; p.Gly57Asp, also known as Gly56Asp when numbered from the mature protein, rs34439278, HbVar ID: 342), also known as Hb J-Meinung, is the most common stable variant found in Taiwanese individuals and has been reported in the heterozygous state in asymptomatic individuals with normal hematological parameters (Zhao 2013, HbVar and references therein). In individuals carrying a beta-+/0 variant, Hb J-Bangkok is not associated with more severe symptoms or hematology than those with the beta-+/0 variant alone (Chang 2002, Zhao 2013). The Hb J-Bangkok variant is reported in ClinVar (Variation ID: 15214) and is observed in the East Asian population at an overall frequency of 0.03% (5/19946 alleles) in the Genome Aggregation Database. The glycine at codon 56 is moderately conserved, computational analyses but are uncertain whether this variant is neutral or deleterious (REVEL: 0.636). Based on available information, this variant is considered likely benign. References: Link to HbVar: https://globin.bx.psu.edu/hbvar/hbvar.html Chang J et al. Hb G-Honolulu (alpha30(B11)Glu-->Gln (alpha2)), Hb J-Meinung (beta56(D7)Gly-->Asp), and beta-thalassemia (codons 41/42 (-TCTT)) in a Taiwanese family. Hemoglobin. 2002 Aug;26(3):325-8. PMID: 12403500. Zhao Y et al. Analysis of clinical phenotypes of compound heterozygotes of Hb J-Bangkok and ß-thalassemia. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2013 Apr;30(2):148-51. PMID: 23568723. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001811154 | SCV004219862 | uncertain significance | not provided | 2024-09-10 | criteria provided, single submitter | clinical testing | The HBB c.170G>A (p.Gly57Asp) variant has been reported in the published literature to have normal stability and oxygen affinity (PMID: 7216820 (1981)), with normal clinical presentation in heterozygotes (PMIDs: 7216820 (1981), 6025242 (1967)). Compound heterozygous individuals carrying this variant and a beta+ thalassemia variant on the other allele presented as beta-thalassemia trait, suggesting this variant did not aggravate the phenotype (PMIDs: 23568723 (2013), 12403500 (2002), 1428942 (1992)). The frequency of this variant in the general population, 0.00025 (5/19946 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000016405 | SCV005076078 | uncertain significance | not specified | 2024-04-16 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.170G>A (p.Gly57Asp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251448 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.170G>A was identified in the literature in heterozygous carriers who were clinically normal (e.g. Blackwell_1966, Pootrakul_1967). It has also been reported in the compound heterozygous state with pathogenic variants in individuals with some features of Beta Thalassemia as well as in clinically normal indivduals (e.g. Honig_1982, Chang_2002, Fucharoen_2001, 2005, Zhang_2017). These reports do not provide unequivocal conclusions about association of the variant with Beta Thalassemia. 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: 12403500, 6252122, 6025242, 5967288, 19631632, 19460936, 20838957, 6859036, 5970505, 5415584, 21599435, 7216820, 15938724, 11422410, 4421749, 7161111, 28407371). ClinVar contains an entry for this variant (Variation ID: 15214). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| OMIM | RCV000016405 | SCV000036673 | benign | not specified | 2017-12-12 | no assertion criteria provided | literature only |