ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.256-2A>G (rs1057516372)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410134 SCV000485546 likely pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2015-12-30 criteria provided, single submitter clinical testing
Invitae RCV000410134 SCV000956936 likely pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2018-08-27 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 3 of the PMM2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in an individual affected with PMM2-related disease (PMID: 21541725). ClinVar contains an entry for this variant (Variation ID: 370282). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PMM2 are known to be pathogenic (PMID: 19862844). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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