NM_001079804.3:c.763C>T

CA401363371

Gene: GAA

Condition: glycogen storage disease II

Inheritance Mode: Autosomal recessive inheritance

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

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

• Met criteria codes: PVS1 PP4 PM2

• Not Met criteria codes: PM3

Expert Panel

Lysosomal Diseases VCEP

Criteria Specification Information

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.

Met criteria codes

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

Not Met criteria codes

• 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.

Approved on: 2020-06-16

Published on: 2020-11-11