ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2417C>T (p.Thr806Met)

gnomAD frequency: 0.00056  dbSNP: rs139850074
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel RCV000542072 SCV004009589 uncertain significance Glycogen storage disease, type II 2023-06-20 reviewed by expert panel curation The NM_000152.5: c.2417C>T variant in GAA is a missense variant predicted to cause substitution of threonine by methionine at amino acid 806 (p.Thr806Met). To our knowledge, this variant has not been reported in the literature in individuals with Pompe disease, and the results of experimental studies are not available. The highest population minor allele frequency in gnomAD v2.1.1 is 0.001189 (42/35310 alleles) in Latino/Admixed American population. This allele frequency meets neither the PM2 allele frequency threshold (<0.001) nor the BS1 allele frequency threshold (>0.005) specified by the ClinGen Lysosomal Diseases VCEP. The computational predictor REVEL gives a score of 0.435 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). There is a ClinVar entry for this variant (Variation ID: 252467). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for Pompe disease due to insufficient evidence. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): BP4. (Classification approved by the ClinGen Lysosomal Diseases VCEP on June 20, 2023).
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000238987 SCV000296876 uncertain significance not specified 2015-10-16 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000725668 SCV000338490 uncertain significance not provided 2016-01-23 criteria provided, single submitter clinical testing
Invitae RCV000542072 SCV000626569 likely benign Glycogen storage disease, type II 2024-01-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000725668 SCV001502250 likely benign not provided 2020-10-01 criteria provided, single submitter clinical testing
GeneDx RCV000725668 SCV001767605 uncertain significance not provided 2022-12-29 criteria provided, single submitter clinical testing Reported previously as part of a thesis project of genetic variation identified among healthy Armenian individuals through exome sequencing (Akopyan, 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 22253258, 19343043)
Genome-Nilou Lab RCV000542072 SCV001810193 uncertain significance Glycogen storage disease, type II 2021-07-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV002519855 SCV003691858 uncertain significance Inborn genetic diseases 2022-04-07 criteria provided, single submitter clinical testing The c.2417C>T (p.T806M) alteration is located in exon 17 (coding exon 16) of the GAA gene. This alteration results from a C to T substitution at nucleotide position 2417, causing the threonine (T) at amino acid position 806 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity Omics RCV000725668 SCV003816202 uncertain significance not provided 2021-08-05 criteria provided, single submitter clinical testing
Natera, Inc. RCV000542072 SCV001455441 uncertain significance Glycogen storage disease, type II 2020-01-17 no assertion criteria provided clinical testing

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