Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| University of Washington Center for Mendelian Genomics, |
RCV000191914 | SCV000246137 | pathogenic | Diamond-Blackfan anemia 15 with mandibulofacial dysostosis | 2015-05-19 | criteria provided, single submitter | research | |
| Labcorp Genetics |
RCV000167574 | SCV001410055 | pathogenic | Diamond-Blackfan anemia 10 | 2019-07-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RPS26 are known to be pathogenic (PMID: 20116044, 23718193). This variant has been observed in an individual affected with Diamond-Blackfan anaemia (PMID: 23718193). ClinVar contains an entry for this variant (Variation ID: 187849). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg87*) in the RPS26 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002433720 | SCV002745467 | pathogenic | Diamond-Blackfan anemia | 2017-07-07 | criteria provided, single submitter | clinical testing | The p.R87* pathogenic mutation (also known as c.259C>T), located in coding exon 3 of the RPS26 gene, results from a C to T substitution at nucleotide position 259. This changes the amino acid from an arginine to a stop codon within coding exon 3. This alteration occurs at amino acid position 87 of coding exon 3, which is the next-to-last exon of the gene, so while it is truncating, the mRNA may escape nonsense mediated decay (NMD). Premature termination codons located either in the last exon or within 50-55 nucleotides upstream of the 3'-most exon-exon junction usually fail to elicit NMD (Maquat LE. Nat. Rev. Mol. Cell Biol. 2004 Feb; 5(2):89-99). However, this mutation has been reported in multiple individuals with a clinical diagnosis of Diamond-Blackfan anemia (Gerrard G et al. Br. J. Haematol. 2013 Aug; 162(4):530-6; Chae H et al. Exp. Mol. Med. 2014 Mar; 46():e88; Gripp KW et al. Am. J. Med. Genet. A. 2014 Sep; 164A(9):2240-9). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
| OMIM | RCV000167574 | SCV000218454 | pathogenic | Diamond-Blackfan anemia 10 | 2014-09-01 | no assertion criteria provided | literature only |