Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756237 | SCV000883985 | likely benign | not provided | 2023-04-19 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000756237 | SCV000889366 | likely benign | not provided | 2020-09-24 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781437 | SCV000919457 | likely benign | not specified | 2018-04-24 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.23A>G (p.Glu8Gly) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 245938 control chromosomes (in gnomAD). This frequency is not higher than expected for a pathogenic variant in HBB causing Hemoglobinopathy (1.2e-05 vs 0.011), allowing no conclusion about variant significance. The variant, c.23A>G has been reported in the literature in a healthy individual in homozygosity (Brancati_1989) as well as in several healthy carriers (e.g. Smith_2016). The variant is known in the literature as a rare polymorphism that has been reported mostly in Southern Italian or of Mexican families (Lacerra 2002). Individuals, who have the variant of interest together with b-thal mutation are likely to have hematological values reflecting their b-thal carrier status. Studies of functional properties confirmed that the variant protein has normal oxygen affinity, cooperativity and Bohr effect with a slightly decreased stability that may have only a marginal role, considering that the variant is not associated with a clinically significant hemolytic process (Roth_1977, Lacerra_2002). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as Likely Benign. |
| OMIM | RCV000016353 | SCV000036621 | other | HEMOGLOBIN G (SAN JOSE) | 2017-12-12 | no assertion criteria provided | literature only |