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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_000152.5(GAA):c.258C>A (p.Pro86=)

CA8814829

282138 (ClinVar)

Gene: GAA
Condition: glycogen storage disease II
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 9c72b762-5be6-4777-9359-162854095e07
Approved on: 2023-12-05
Published on: 2023-12-07

HGVS expressions

NM_000152.5:c.258C>A
NM_000152.5(GAA):c.258C>A (p.Pro86=)
NC_000017.11:g.80104844C>A
CM000679.2:g.80104844C>A
NC_000017.10:g.78078643C>A
CM000679.1:g.78078643C>A
NC_000017.9:g.75693238C>A
NG_009822.1:g.8289C>A
ENST00000302262.8:c.258C>A
ENST00000302262.7:c.258C>A
ENST00000390015.7:c.258C>A
ENST00000570803.5:c.258C>A
ENST00000577106.5:c.258C>A
NM_000152.3:c.258C>A
NM_001079803.1:c.258C>A
NM_001079804.1:c.258C>A
NM_000152.4:c.258C>A
NM_001079803.2:c.258C>A
NM_001079804.2:c.258C>A
NM_001079803.3:c.258C>A
NM_001079804.3:c.258C>A
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Likely Benign

Met criteria codes 3
BS1 BP7 BP4
Not Met criteria codes 5
PS3 BA1 PM2 BS3 BS2

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Lysosomal Diseases VCEP
The NM_000152.5: c.258C>A (p.Pro86=) variant in GAA is a synonymous variant with a highest population minor allele frequency in gnomAD v4.0.0 of 0.00509 (382/75054 alleles) in the African/African American population, which is higher than the ClinGen Lysosomal Diseases (LD) VCEP’s threshold for BS1 (>0.005), meeting this criterion (BS1). The variant is not predicted to impact splicing; the nucleotide is not conserved (BP4, BP7). There is a ClinVar entry for this variant (Variation ID: 282138). In summary, this variant meets the criteria to be classified as likely benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): BS1, BP4, BP7. (Classification approved by the ClinGen Lysosomal Diseases VCEP on December 5, 2023).
Met criteria codes
BS1
The NM_000152.5: c.258C>A (p.Pro86=) variant in GAA is a synonymous variant with a highest population minor allele frequency in gnomAD v4.0.0 of 0.00509 (382/75054 alleles) in the African/African American population, which is higher than the ClinGen Lysosomal Diseases (LD) VCEP’s threshold for BS1 (>0.005), meeting this criterion (BS1).
BP7
A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved.
BP4
SpliceAI predicts that the variant has no impact on splicing (BP4).
Not Met criteria codes
PS3
No functional study for this variant.
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
See BS1
BS3
No functional study for this variant.
BS2
There are 3 individuals homozygous for the variant in gnomAD v4.0.0; however, no GAA activities are provided.
Curation History
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