ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2316G>T (p.Trp772Cys)

dbSNP: rs1057524664
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel RCV000675111 SCV002583374 uncertain significance Glycogen storage disease, type II 2022-09-19 reviewed by expert panel curation The NM_000152.5:c.2316G>T variant in GAA is a missense variant predicted to cause substitution of Tryptophan by Cysteine at amino acid 772 (p.Trp772Cys). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). To our knowledge, the results of functional assays have not been reported for this variant and this variant has not been reported in the literature in any individuals with Pompe disease. The computational predictor REVEL gives a score of 0.942 which is above the threshold of 0.7, evidence that correlates with impact to GAA function (PP3). Another missense variant c.2314T>C (p.Trp772Arg) (PMID: 31619483, 18757064, ClinVar ID: 552527) in the same codon has been classified as likely pathogenic for Pompe disease by the ClinGen LSD VCEP (PM5_Supporting). There is a ClinVar entry for this variant (Variation ID: 392862, 2 star review status) with 3 submitters classifying the variant as Uncertain Significance. In summary, this variant meets the criteria to be classified as a Variant of Uncertain Significance for Pompe disease based on the ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Storage Disorders Variant Curation Expert panel (specifications Version 2.0): PP3, PM2_Supporting, PM5_Supporting.
GeneDx RCV000439307 SCV000536196 uncertain significance not provided 2020-05-20 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Counsyl RCV000675111 SCV000800659 uncertain significance Glycogen storage disease, type II 2018-02-13 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000675111 SCV001810187 uncertain significance Glycogen storage disease, type II 2021-07-22 criteria provided, single submitter clinical testing

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