ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2040+17G>A (rs534129336)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000610426 SCV000714877 likely benign not specified 2018-02-15 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000610426 SCV001363619 uncertain significance not specified 2019-03-25 criteria provided, single submitter clinical testing Variant summary: GAA c.2040+17G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00013 in 253278 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (0.00013 vs 0.0042), allowing no conclusion about variant significance. The variant, c.2040+17G>A has been reported in the literature in a newborn screening conducted in Taiwan, without strong evidence of causality (Labrousse_2010). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.

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