Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002444558 | SCV002732751 | pathogenic | Diamond-Blackfan anemia | 2014-05-27 | criteria provided, single submitter | clinical testing | The p.E82* pathogenic mutation (also known as c.244G>T), located in coding exon 4 of the RPL5 gene, results from a G to T substitution at nucleotide position 244. This changes the amino acid from a to a stop codon within coding exon 4. In one study, this mutation was reported in a mother and daughter with DBA. The 39-year-old mother was diagnosed at 5 years of age and had growth retardation, osteoporosis, thumb abnormalities, and severe hepatic iron overload. Her 10-year-old daughter had intrauterine growth retardation and fetal distress, was diagnosed at birth, and had ventricular septal defect, cleft palate, clinodactyly, Cathie facies, growth retardation, vitamin D deficiency, and severe hepatic iron overload. Both had high erythrocyte adenosine deaminase, and while the mother was steroid responsive the daughter developed secondary steroid resistance (Gerrard G et al. Br J Haematol. 2013;162(4):530-536). 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 | RCV000087038 | SCV000119852 | pathogenic | Diamond-Blackfan anemia 6 | 2013-08-01 | no assertion criteria provided | literature only |