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]

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Variant: NM_000152.4(GAA):c.93_95del (p.Leu32del)

Curation Version - 1.1
Curation History
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CA628018663

526535 (ClinVar)

Gene: GAA

Condition: glycogen storage disease II

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6b399c3b-9524-48b9-a750-034bad29298b

Approved on: 2020-02-14

Published on: 2020-05-26

HGVS expressions

NM_000152.4:c.93_95del

NM_000152.4(GAA):c.93_95del (p.Leu32del)

NC_000017.11:g.80104679_80104681del

CM000679.2:g.80104679_80104681del

NC_000017.10:g.78078478_78078480del

CM000679.1:g.78078478_78078480del

NC_000017.9:g.75693073_75693075del

NG_009822.1:g.8124_8126del

ENST00000570803.6:c.93_95del

ENST00000572080.2:c.93_95del

ENST00000577106.6:c.93_95del

ENST00000302262.8:c.93_95del

ENST00000302262.7:c.93_95del

ENST00000390015.7:c.93_95del

ENST00000570803.5:c.93_95del

ENST00000577106.5:c.93_95del

NM_000152.3:c.93_95del

NM_001079803.1:c.93_95del

NM_001079804.1:c.93_95del

NM_001079803.2:c.93_95del

NM_001079804.2:c.93_95del

NM_000152.5:c.93_95del

NM_001079803.3:c.93_95del

NM_001079804.3:c.93_95del

Uncertain Significance

BP4 PM4_Supporting PM2

Evidence Links 0

Expert Panel

Lysosomal Diseases VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Lysosomal Diseases VCEP

This variant, c.93_95del (p.Leu32del), is expected to result in an in frame single amino acid deletion of GAA. Therefore, PM4_Supporting can be applied based on the specifications of the ClinGen LSD VCEP. The highest population minor allele frequency for this variant in gnomAD is 0.0001149 in Africans, which meets the ClinGen LSD VCEP’s threshold for PM2. To our knowledge, this variant has not been reported in the literature in individuals with Pompe disease, and results of experimental studies are not available. PROVEAN and Mutation Taster predict that the variant will have no impact on GAA function. Therefore, BP4 can be applied. In summary, this variant meets the criteria to be classified as a Variant of Unknown Significance for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: PM2, PM4_Supporting, BP4.

BP4

Multiple lines of computational evidence predict that this variant has no impact on the gene product. The PROVEAN score is -0.65 (not meeting the threshold of -2.5 for deleterious), and Mutation Taster predicts that this variant is a "polymorphism". This data meets the BP4 criterion as specified by the ClinGen LSD VCEP.

PM4_Supporting

This variant results in an inframe single amino acid deletion in GAA, meeting the ClinGen LSD VCEP's criteria for PM4_Supporting.

PM2

The highest population minor allele frequency in gnomAD is 0.0001149 (African) which is lower than the ClinGen LSD VCEP threshold (<0.001) for PM2, meeting this criterion.

Curation History

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