ClinVar Miner

Submissions for variant NM_007215.4(POLG2):c.796-2A>G

dbSNP: rs2144187906
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001755596 SCV002005163 uncertain significance not provided 2019-01-31 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); Destroys the canonical splice acceptor site in intron 3 and is predicted to cause abnormal gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001755596 SCV002208289 pathogenic not provided 2023-03-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1318948). Disruption of this splice site has been observed in individual(s) with progressive external ophthalmoplegia with mitochondrial DNA deletions (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 3 of the POLG2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in POLG2 are known to be pathogenic (PMID: 28078310, 29625556).

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