Variant: NM_000152.5(GAA):c.352C>T (p.Gln118Ter)

CA401360858

553894 (ClinVar)

Gene: GAA

Condition: glycogen storage disease II

Inheritance Mode: Autosomal recessive inheritance

UUID: ab2f63ee-a9db-4f17-959b-d28f30a191aa

HGVS expressions

NM_000152.5:c.352C>T
NM_000152.5(GAA):c.352C>T (p.Gln118Ter)
NC_000017.11:g.80104938C>T
CM000679.2:g.80104938C>T
NC_000017.10:g.78078737C>T
CM000679.1:g.78078737C>T
NC_000017.9:g.75693332C>T
NG_009822.1:g.8383C>T
NM_000152.3:c.352C>T
NM_001079803.1:c.352C>T
NM_001079804.1:c.352C>T
NM_000152.4:c.352C>T
NM_001079803.2:c.352C>T
NM_001079804.2:c.352C>T
NM_001079803.3:c.352C>T
NM_001079804.3:c.352C>T
ENST00000302262.7:c.352C>T
ENST00000390015.7:c.352C>T
ENST00000570803.5:c.352C>T
ENST00000577106.5:c.352C>T

Pathogenic

• Met criteria codes: PP4 PM2 PVS1

Expert Panel

Lysosomal Diseases VCEP

Criteria Specification Information

Evidence submitted by expert panel

Lysosomal Diseases VCEP

This variant, c.352C>T (p.Gln118Ter), is a nonsense variant that is predicted to cause nonsense mediated decay and lack of gene product, meeting PVS1. The variant is absent in gnomAD v2.1.1, meeting PM2. It has been reported in a patient with Pompe disease that meets the ClinGen LSD VCEP’s PP4 specifications (PMID 22252923, personal communication). There is a ClinVar entry for this variant (Variation ID: 553894; 1 star review status) with one submitter classifying the variant as likely pathogenic. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: PVS1, PM2, PP4.

Met criteria codes

• PP4: This variant has been reported in a patient with <30% normal GAA activity in skin fibroblasts (PMID 22252923, personal communication), meeting PP4.
• PM2: This variant is absent in gnomAD v2.1.1.
• PVS1: This is a nonsense variant which is predicted to cause nonsense mediated decay resulting in no gene product. Therefore, PVS1 can be applied.

Approved on: 2020-05-19

Published on: 2020-06-03