NM_000152.5(GAA):c.836G>A (p.Trp279Ter) AND Glycogen storage disease, type II

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 23, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001193013.8

Allele description [Variation Report for NM_000152.5(GAA):c.836G>A (p.Trp279Ter)]

NM_000152.5(GAA):c.836G>A (p.Trp279Ter)

Gene:

GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.836G>A (p.Trp279Ter)

HGVS:

NC_000017.11:g.80107700G>A
NG_009822.1:g.11145G>A
NM_000152.5:c.836G>AMANE SELECT
NM_001079803.3:c.836G>A
NM_001079804.3:c.836G>A
NP_000143.2:p.Trp279Ter
NP_001073271.1:p.Trp279Ter
NP_001073272.1:p.Trp279Ter
LRG_673t1:c.836G>A
LRG_673:g.11145G>A
NC_000017.10:g.78081499G>A
NM_000152.4:c.836G>A

Protein change:

W279*

Links:

dbSNP: rs2039122730

NCBI 1000 Genomes Browser:

rs2039122730

Molecular consequence:

NM_000152.5:c.836G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001079803.3:c.836G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001079804.3:c.836G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Glycogen storage disease, type II (GSD2)
Synonyms:: ACID ALPHA-GLUCOSIDASE DEFICIENCY; GLYCOGENOSIS, GENERALIZED, CARDIAC FORM; GSD II; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009290; MedGen: C0017921; Orphanet: 365; OMIM: 232300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001361537	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Sep 23, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22644586, 29122469, 23463700 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001361537

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Sep 23, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Update of the pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants.

Kroos M, Hoogeveen-Westerveld M, Michelakakis H, Pomponio R, Van der Ploeg A, Halley D, Reuser A; GAA Database Consortium..

Hum Mutat. 2012 Aug;33(8):1161-5. doi: 10.1002/humu.22108. Epub 2012 May 29.

PubMed [citation]

PMID:: 22644586

Sensitivity of whole exome sequencing in detecting infantile- and late-onset Pompe disease.

Mori M, Haskell G, Kazi Z, Zhu X, DeArmey SM, Goldstein JL, Bali D, Rehder C, Cirulli ET, Kishnani PS.

Mol Genet Metab. 2017 Dec;122(4):189-197. doi: 10.1016/j.ymgme.2017.10.008. Epub 2017 Oct 17.

PubMed [citation]

PMID:: 29122469
PMCID:: PMC5907499

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361537.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: GAA c.836G>A (p.Trp279X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249974 control chromosomes (gnomAD). c.836G>A has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) (Dubrovsky_2013, Mori_2017). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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