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_000152.4(GAA):c.668G>A (p.Arg223His)

Curation Version - 1.2
Curation History
JSON LD for Version 1.2

CA145791

92488 (ClinVar)

Gene: GAA

Condition: glycogen storage disease II

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 5209e127-3f93-4166-b5f2-d98600bdd5c9

Approved on: 2020-01-22

Published on: 2020-05-19

HGVS expressions

NM_000152.4:c.668G>A

NM_000152.4(GAA):c.668G>A (p.Arg223His)

NC_000017.11:g.80105870G>A

CM000679.2:g.80105870G>A

NC_000017.10:g.78079669G>A

CM000679.1:g.78079669G>A

NC_000017.9:g.75694264G>A

NG_009822.1:g.9315G>A

NM_000152.3:c.668G>A

NM_001079803.1:c.668G>A

NM_001079804.1:c.668G>A

NM_001079803.2:c.668G>A

NM_001079804.2:c.668G>A

NM_000152.5:c.668G>A

NM_001079803.3:c.668G>A

NM_001079804.3:c.668G>A

ENST00000302262.7:c.668G>A

ENST00000390015.7:c.668G>A

ENST00000570803.5:c.668G>A

Benign

BA1

Evidence Links 0

Expert Panel

Lysosomal Diseases VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Lysosomal Diseases VCEP

The highest continental population minor allele frequency for c.668G>A (p.Arg223His) in gnomAD v2.1.1 is 0.74034 in the European non-Finnish population. This is higher than the ClinGen LSD VCEP’s BA1 threshold (>0.01), therefore meeting the BA1 criterion. There is a ClinVar entry for this variant (Variation ID: 92488; 2 star review status) with six submitters classifying the variant as benign, and one as likely benign. In summary, this variant meets the criteria to be classified as benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: BA1.

BA1

The highest population minor allele frequencies in gnomAD are 0.7786 (Ashkenazi Jewish), 0.7541 (European Finnish), and 0.7403 (European non-Finnish). These allele frequencies are higher than the ClinGen LSD VCEP's threshold (>0.01) for BA1. Therefore, the allele frequency data for this variant meets the BA1 criterion, as specified by the ClinGen LSD VCEP.

Curation History

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