Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002428064 | SCV002730182 | likely pathogenic | Diamond-Blackfan anemia | 2018-11-01 | criteria provided, single submitter | clinical testing | The p.C74Y variant (also known as c.221G>A), located in coding exon 3 of the RPS26 gene, results from a G to A substitution at nucleotide position 221. The cysteine at codon 74 is replaced by tyrosine, an amino acid with highly dissimilar properties. This variant has been determined to be the result of a de novo mutation or germline mosaicism in one family with an isolated case of Diamond-Blackfan anemia. A different alteration at the same position (p.C74S) has been reported in twin boys with Diamond-Blackfan anemia (Wan Y et al. Int. J. Hematol., 2016 Oct;104:430-9). Based on internal structural analysis, this variant is anticipated to disrupt a region of known function (Yamamoto H et al. EMBO J., 2015 Dec;34:3042-58). This variant was not reported in the gnomAD database, with coverage at this position. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |