Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000779550 | SCV000916220 | uncertain significance | Dihydropyrimidinase deficiency | 2018-10-22 | criteria provided, single submitter | clinical testing | The DPYS c.242A>G (p.Asp81Gly) variant is a missense variant has been reported in one study, in which it is found in a compound heterozygous state in one individual with dihydropyrimidinase deficiency (van Kuilenburg et al. 2010). The patient was reported to have intellectual disability but was negative for gastrointentinal problems and any other neurological symptoms. The p.Asp81Gly variant was absent from 90 controls, and is not found in the 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium, or the Genome Aggregation Database. Functional studies demonstrated that the p.Asp81Gly variant resulted in less than 0.2% DHP activity and no detected activity in E.coi and 293FT cells, respectively. Analysis of the crystal structure suggested that the Asp81 residue played a critical role in connections between protein domains (van Kuilenburg et al. 2010; Hishinuma et al. 2017). Based on the evidence, the p.Asp81Gly variant is classified as a variant of unknown significance but suspicious for pathogenicity for dihydropyrimidinase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |