ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.131G>T (p.Gly44Val)

gnomAD frequency: 0.00017  dbSNP: rs550609502
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel RCV000278138 SCV001371698 uncertain significance Glycogen storage disease, type II 2023-06-20 reviewed by expert panel curation The NM_000152.5:c.131G>T variant in GAA is predicted to result in the substitution of glycine by valine at amino acid 44 (p.Gly44Val). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00025 (32/126504 alleles) in the European non-Finnish population, which is lower than the ClinGen LSD VCEP’s threshold for PM2_Supporting (<0.001), meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.245 which is below the threshold of 0.5, evidence that does not predict a damaging effect on GAA function. No impact on splicing is predicted by SpliceAI (BP4). To our knowledge, this variant has not been reported in the literature in individuals with Pompe disease, and the results of functional studies are not available. There is a ClinVar entry for this variant (Variation ID: 325774). 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 LSD VCEP: PM2_Supporting, BP4. (Classification approved by the ClinGen Lysosomal Diseases VCEP on June 20, 2023).
Illumina Laboratory Services, Illumina RCV000278138 SCV000407254 uncertain significance Glycogen storage disease, type II 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000278138 SCV000626505 likely benign Glycogen storage disease, type II 2024-01-17 criteria provided, single submitter clinical testing
GeneDx RCV000786314 SCV001779468 uncertain significance not provided 2021-01-19 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Mayo Clinic Laboratories, Mayo Clinic RCV000786314 SCV002541438 uncertain significance not provided 2023-03-28 criteria provided, single submitter clinical testing BP4, PM2
Fulgent Genetics, Fulgent Genetics RCV000278138 SCV002783621 uncertain significance Glycogen storage disease, type II 2021-11-01 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000786314 SCV003828481 uncertain significance not provided 2021-09-22 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000786314 SCV000925084 uncertain significance not provided 2017-09-07 no assertion criteria provided provider interpretation
Natera, Inc. RCV000278138 SCV001463465 uncertain significance Glycogen storage disease, type II 2020-01-24 no assertion criteria provided clinical testing

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