ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.93_95del (p.Leu32del)

dbSNP: rs1278892703
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel RCV000631080 SCV001371742 uncertain significance Glycogen storage disease, type II 2023-05-28 reviewed by expert panel curation The NM_000152.5:c.93_95del variant in GAA is predicted to cause a change in the length of the protein (p.Leu32del) due to an in-frame deletion of one amino acid in a non-repeat region (PM4_Supporting). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0001149 (1/8700 alleles) in the African population, which is lower than the ClinGen LSD VCEP’s threshold for PM2_Supporting (<0.001), meeting this criterion (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in individuals with Pompe disease, and results of experimental studies are not available. PROVEAN and Mutation Taster predict that the variant will have no impact on GAA function. SpliceAI predicts no impact on splicing (BP4). There is a ClinVar entry for this variant (Variation ID: 526535). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): PM2_Supporting, PM4_Supporting, BP4. (Classification approved by the ClinGen Lysosomal Diseases VCEP on May 28, 2023)
Labcorp Genetics (formerly Invitae), Labcorp RCV000631080 SCV000752073 uncertain significance Glycogen storage disease, type II 2022-03-23 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 526535). This variant has not been reported in the literature in individuals affected with GAA-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant, c.93_95del, results in the deletion of 1 amino acid(s) of the GAA protein (p.Leu32del), but otherwise preserves the integrity of the reading frame.

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