ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.546+5G>T (rs756024023)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673997 SCV000799265 uncertain significance Glycogen storage disease, type II 2018-04-06 criteria provided, single submitter clinical testing
Invitae RCV000673997 SCV000964244 likely pathogenic Glycogen storage disease, type II 2018-09-24 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the GAA gene. It does not directly change the encoded amino acid sequence of the GAA protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs756024023, ExAC 0.04%). This variant has been observed in two individuals with low alpha-glucosidase enzyme activity, findings that are highly specific for Pompe disease (PMID: 21232767). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. 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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