ClinVar Miner

Submissions for variant NM_080916.3(DGUOK):c.592-4_592-3del

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV003318801 SCV004022551 pathogenic not provided 2022-12-23 criteria provided, single submitter clinical testing Observed with a pathogenic variant in a patient with clinical features of DGUOK-related deoxyguanosine kinase deficiency, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Dimmock et al., 2008); Non-canonical splice site variant demonstrated to result in loss of function (Ji et al., 2010); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19900589, 18205204)
Labcorp Genetics (formerly Invitae), Labcorp RCV003318801 SCV004292608 pathogenic not provided 2023-09-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 5 and introduces a premature termination codon (PMID: 19900589). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 2574219). This variant has been observed in individual(s) with mitochondrial DNA depletion syndrome (PMID: 18205204, 19900589). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change falls in intron 4 of the DGUOK gene. It does not directly change the encoded amino acid sequence of the DGUOK protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product.
Fulgent Genetics, Fulgent Genetics RCV005029978 SCV005659362 likely pathogenic Mitochondrial DNA depletion syndrome 3 (hepatocerebral type); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4; Portal hypertension, noncirrhotic, 1 2024-05-09 criteria provided, single submitter clinical testing

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