ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1888+10_1888+11insC (rs748036956)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479968 SCV000572460 likely benign not specified 2016-12-23 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000675233 SCV000709496 uncertain significance not provided 2017-06-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000479968 SCV000917392 uncertain significance not specified 2018-03-13 criteria provided, single submitter clinical testing Variant summary: GAA c.1888+10_1888+11insC 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. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant is found in gnomAD dataset exclusively in individuals of African descent at a frequency of 0.00076 (16/21150 chrs tested). This frequency is not higher than expected for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (0.00076 vs 0.0042), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1888+10_1888+11insC in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) and no experimental evidence demonstrating its impact on protein function have 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. Another lab classified the variant as VUS. Based on the evidence outlined above, the variant was classified as uncertain significance.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000675233 SCV000800879 likely benign not provided 2017-05-17 no assertion criteria provided clinical testing

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