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]
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  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.
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  • See Evidence submitted by expert panel for details.

Variant: NM_001079804.3:c.444C>G

CA401361416

1327503 (ClinVar)

Gene: GAA
Condition: glycogen storage disease II
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: e52579bd-73f1-4105-a1db-7265b9bf9b8b

HGVS expressions

NM_001079804.3:c.444C>G
NC_000017.11:g.80105030C>G
CM000679.2:g.80105030C>G
NC_000017.10:g.78078829C>G
CM000679.1:g.78078829C>G
NC_000017.9:g.75693424C>G
NG_009822.1:g.8475C>G
ENST00000302262.8:c.444C>G
ENST00000302262.7:c.444C>G
ENST00000390015.7:c.444C>G
ENST00000570803.5:c.444C>G
ENST00000577106.5:c.444C>G
NM_000152.3:c.444C>G
NM_001079803.1:c.444C>G
NM_001079804.1:c.444C>G
NM_000152.4:c.444C>G
NM_001079803.2:c.444C>G
NM_001079804.2:c.444C>G
NM_000152.5:c.444C>G
NM_001079803.3:c.444C>G
NM_000152.5(GAA):c.444C>G (p.Tyr148Ter)

Pathogenic

Met criteria codes 3
PM2_Supporting PVS1 PP4
Not Met criteria codes 1
PM3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Lysosomal Diseases VCEP
The NM_000152.5:c.444C>G (p.Tyr148Ter) variant in GAA is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 2/20, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). One patient, with late onset Pompe disease, has been reported who responded to enzyme replacement therapy and had muscle histology consistent with Pompe disease (PMID 25093132)(PP4). This patient is compound heterozygous, phase unknown, for the variant and c.2238G>C (p.Trp746Cys). The allelic data for this patient will be used in the assessment of p.Trp746Cys and is not included here to avoid circular logic. The c.444C>G (p.Tyr148Ter) variant is absent in gnomAD v2.1.1 (PM2_Supporting). There is no ClinVar entry for this variant. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. ACMG/AMP criteria met, as specified by the ClinGen LSD VCEP (Specification Version 2.0): PVS1, PP4, PM2_Supporting (Approved by the ClinGen LSD VCEP - Oct. 19th, 2021)
Met criteria codes
PM2_Supporting
This variant is absent in gnomAD v2.1.1 (PM2_Supporting).
PVS1
The NM_000152.5:c.444C>G (p.Tyr148Ter) variant in GAA is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 2/20, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
PP4
One patient, with late onset Pompe disease, has been reported who responded to enzyme replacement therapy and had muscle histology consistent with Pompe disease (PMID 25093132)(PP4).
Not Met criteria codes
PM3
One patient with Pompe disease has been reported with this variant. This patient is compound heterozygous, phase unknown, for the variant and c.2238G>C (p.Trp746Cys). The allelic data for this patient will be used in the assessment of p.Trp746Cys and is not included here to avoid circular logic.
Approved on: 2021-12-02
Published on: 2022-11-29
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