Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000152.5(GAA):c.169C>T (p.Gln57Ter)

CA16041879

370124 (ClinVar)

Gene: GAA
Condition: glycogen storage disease II
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: a9a94504-8171-4e5e-98ae-30d711747395
Approved on: 2023-11-06
Published on: 2024-04-12

HGVS expressions

NM_000152.5:c.169C>T
NM_000152.5(GAA):c.169C>T (p.Gln57Ter)
NC_000017.11:g.80104755C>T
CM000679.2:g.80104755C>T
NC_000017.10:g.78078554C>T
CM000679.1:g.78078554C>T
NC_000017.9:g.75693149C>T
NG_009822.1:g.8200C>T
ENST00000570803.6:c.169C>T
ENST00000572080.2:c.169C>T
ENST00000577106.6:c.169C>T
ENST00000302262.8:c.169C>T
ENST00000302262.7:c.169C>T
ENST00000390015.7:c.169C>T
ENST00000570803.5:c.169C>T
ENST00000577106.5:c.169C>T
NM_000152.3:c.169C>T
NM_001079803.1:c.169C>T
NM_001079804.1:c.169C>T
NM_000152.4:c.169C>T
NM_001079803.2:c.169C>T
NM_001079804.2:c.169C>T
NM_001079803.3:c.169C>T
NM_001079804.3:c.169C>T
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Pathogenic

Met criteria codes 3
PP4_Moderate PM2_Supporting PVS1
Not Met criteria codes 1
PM3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Lysosomal Storage Disorders Variant Curation Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Lysosomal Diseases VCEP
The NM_000152.5:c.169C>T (p.Gln57Ter) variant in GAA is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 2 (there are 20 exons in GAA), leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). One individual with symptoms consistent with late-onset Pompe disease and deficient GAA activity in lymphocytes has been reported who is compound heterozygous for the variant and a missense variant, c,655G>A (p.Gly219Arg), in GAA (PMID 29124014) (PP4_Moderate). The allelic data for this patient will be used in the classification of p.Gly219Arg and is not included here to avoid circular logic. This variant is absent in gnomAD v2.1.1. (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (Specifications Version 2.0): PVS1, PP4_Moderate, PM2_Supporting. (Classification approved by the ClinGen Lysosomal Diseases VCEP on November 6, 2023).
Met criteria codes
PP4_Moderate
One individual with symptoms consistent with late-onset Pompe disease and <10% GAA activity in lymphocytes (PMID 29124014) (PP4_Moderate).
PM2_Supporting
This variant is not in gnomAD v2.1.1.
PVS1
The NM_000152.5:c.169C>T (p.Gln57Ter) variant in GAA is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 2 (there are 20 exons in GAA), leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
Not Met criteria codes
PM3
One individual with Pompe disease has been reported who is compound heterozygous for the variant and a missense variant, c,655G>A (p.Gly219Arg), in GAA (PMID 29124014). The allelic data for this patient will be used in the classification of p.Gly219Arg and is not included here to avoid circular logic. PM3 is not met at the current time.
Curation History
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