ClinVar Miner

Submissions for variant NM_080916.3(DGUOK):c.444-11C>G

gnomAD frequency: 0.00003  dbSNP: rs536746349
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478803 SCV000568226 pathogenic not provided 2017-02-02 criteria provided, single submitter clinical testing The c.444-11 C>G splice site variant in the DGUOK gene has been previously reported in association with deoxyguanosine kinase deficiency in a severely affected infant who also harbored a frameshift variant on the opposite allele (Dimmock et al., 2008). Multiple in silico analyses predict this variant generates a new acceptor site in intron 3 and greatly reduces the function of the natural splice acceptor site. Transcript and protein analyses showed the mRNA transcript derived from an allele harboring the c.444-11 C> G variant is absent, and the amount of DGUOK protein is significantly reduced (Ronchi et al., 2013). In summary, c.444-11 C>G is interpreted to be a pathogenic variant.
Eurofins Ntd Llc (ga) RCV000478803 SCV000861194 likely pathogenic not provided 2018-05-07 criteria provided, single submitter clinical testing
Invitae RCV000478803 SCV002316737 uncertain significance not provided 2022-06-02 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the DGUOK gene. It does not directly change the encoded amino acid sequence of the DGUOK protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with mitochondrial DNA depletion syndrome (PMID: 18205204, 23043144). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 253069). Studies have shown that this variant alters DGUOK gene expression (PMID: 23043144). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000239560 SCV000297867 pathogenic Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 2016-08-18 no assertion criteria provided literature only

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