Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001079804.3:c.763C>T

CA401363371

Gene: GAA (HGNC:2548)

Condition: glycogen storage disease II (MONDO:0009290)

Inheritance Mode: Autosomal recessive inheritance

UUID: 24039e0f-56fe-4560-913a-4fc9c4967106

Approved on: 2020-06-16

Published on: 2020-11-11

HGVS expressions

NM_001079804.3:c.763C>T

NC_000017.11:g.80107627C>T

CM000679.2:g.80107627C>T

NC_000017.10:g.78081426C>T

CM000679.1:g.78081426C>T

NC_000017.9:g.75696021C>T

NG_009822.1:g.11072C>T

NM_000152.3:c.763C>T

NM_001079803.1:c.763C>T

NM_001079804.1:c.763C>T

NM_000152.4:c.763C>T

NM_001079803.2:c.763C>T

NM_001079804.2:c.763C>T

NM_000152.5:c.763C>T

NM_001079803.3:c.763C>T

ENST00000302262.7:c.763C>T

ENST00000390015.7:c.763C>T

ENST00000570803.5:c.763C>T

Pathogenic

PP4 PM2 PVS1

PM3

Evidence Links 2

Expert Panel

Lysosomal Diseases VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Lysosomal Diseases VCEP

This variant, c.763C>T (p.Gln255Ter), is a nonsense variant that is predicted to result in nonsense medicated decay and lack of gene product, meeting PVS1. The variant is absent in gnomAD v2.1.1, meeting PM2. It has been reported in trans with c.670C > T (p.Arg224Trp) in an individual with infantile-onset Pompe disease who meets the ClinGen LSD VCEP’s specifications for PP4 (PMID 25026126). The in trans data from this patient was used in the assessment of p.Arg224Trp, and was not included here in order to avoid circular logic. It was also found in a heterozygote, identified by newborn screening (PMID 23430949). There is no ClinVar entry for this variant. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific criteria applied, as specified by the ClinGen LSD VCEP: PVS1, PM2, PP4.

PP4

One individual with this variant has been reported with <1% residual GAA activity (PMID 25026126), meeting PP4.

PM2

This variant is absent in gnomAD v2.1.1, meeting PM2.

PVS1

This is a nonsense variant which is predicted to result in nonsense mediated decay and lack of gene product, meeting PVS1.

PM3

This variant has been reported in trans with c.670C > T (p.Arg224Trp) in an individual with infantile-onset Pompe disease who meets the ClinGen LSD VCEP’s specifications for PP4 (PMID 25026126). The in trans data from this patient was used in the assessment of p.Arg224Trp, and was not included here in order to avoid circular logic. Therefore, PM3 is not met based on currently available evidence.

PubMed:25026126

PubMed:23430949

Curation History

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