ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.736del (p.Leu246fs)

dbSNP: rs886043920
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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 RCV000410911 SCV001371727 likely pathogenic Glycogen storage disease, type II 2023-07-18 reviewed by expert panel curation The NM_000152.5:c.736del (p.Leu246PhefsTer22) variant in GAA is a frameshift variant predicted to cause a premature stop codon leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The variant is absent in gnomAD v2.1.1. (PM2_Supporting). One patient with limb girdle muscular dystrophy was reported to be compound heterozygous for c.736delC and another variant in GAA that has been classified by the ClinGen LD VCEP as pathogenic, c.546G>A; the phase is unknown. However, because no aditional information is available to support the diagnosis of Pompe disease, such as GAA deficiency, there is insufficient evidence to apply PM3 at this time. . There is a ClinVar entry for this variant (Variation ID: 288505. In summary, this variant meets the criteria to be classified as likely pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP Specifications Version 2.0): PVS1, PM2_Supporting. (Classification approved by the ClinGen Lysosomal Diseases VCEP on July 18, 2023).
Eurofins Ntd Llc (ga) RCV000726173 SCV000701280 pathogenic not provided 2016-06-06 criteria provided, single submitter clinical testing
Invitae RCV000410911 SCV000752054 pathogenic Glycogen storage disease, type II 2022-06-28 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 288505). This variant has not been reported in the literature in individuals affected with GAA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu246Phefs*22) in the GAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000410911 SCV000486042 likely pathogenic Glycogen storage disease, type II 2016-03-18 no assertion criteria provided clinical testing

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