Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics Munich, |
RCV000578318 | SCV000680186 | pathogenic | Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) | 2017-11-08 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000578318 | SCV000915925 | uncertain significance | Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) | 2017-06-23 | criteria provided, single submitter | clinical testing | The DGUOK c.155C>T (p.Ser52Phe) variant has been reported in one study in which it was found in two patients with DGUOK-related mitochondrial DNA depletion syndrome including in one in a homozygous and in one in a compound heterozygous state with a frameshift variant (Freisinger et al. 2006). The p.Ser52Phe variant was absent from 50 control samples and is reported at a frequency of 0.00001 in the European (non-Finnish) population of the Genome Aggregation Database, but this is based on one allele only in an area of good sequence coverage so it is presumed to be rare. The Ser52 residue is highly conserved. Based on the evidence, the p.Ser52Phe variant is classified as a variant of unknown significance but suspicious for pathogenicity for mitochondrial DNA depletion syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004767413 | SCV005381776 | uncertain significance | not specified | 2024-08-26 | criteria provided, single submitter | clinical testing | Variant summary: DGUOK c.155C>T (p.Ser52Phe) results in a non-conservative amino acid change located in the Deoxynucleoside kinase domain (IPR031314) of 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 4e-06 in 251462 control chromosomes. c.155C>T has been reported in the literature in two individuals affected with Hepatocerebral Mitochondrial DNA Depletion Syndrome (Freisinger_2006). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 16908739). ClinVar contains an entry for this variant (Variation ID: 488490). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |