NM_000152.5(GAA):c.502C>T (p.Arg168Trp) AND Glycogen storage disease, type II

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Jan 19, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001044499.9

Allele description [Variation Report for NM_000152.5(GAA):c.502C>T (p.Arg168Trp)]

NM_000152.5(GAA):c.502C>T (p.Arg168Trp)

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.502C>T (p.Arg168Trp)

HGVS:

NC_000017.11:g.80105088C>T
NG_009822.1:g.8533C>T
NM_000152.5:c.502C>TMANE SELECT
NM_001079803.3:c.502C>T
NM_001079804.3:c.502C>T
NP_000143.2:p.Arg168Trp
NP_001073271.1:p.Arg168Trp
NP_001073272.1:p.Arg168Trp
LRG_673t1:c.502C>T
LRG_673:g.8533C>T
NC_000017.10:g.78078887C>T
NC_000017.10:g.78078887C>T
NM_000152.3:c.502C>T

Protein change:

R168W

Links:

dbSNP: rs777473001

NCBI 1000 Genomes Browser:

rs777473001

Molecular consequence:

NM_000152.5:c.502C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001079803.3:c.502C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001079804.3:c.502C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001208300	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 19, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21488292, 25526786, 30155607, 28492532
SCV002027216	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002091926	Natera, Inc.	no assertion criteria provided	Uncertain significance (Dec 14, 2020)	germline	clinical testing
SCV002789176	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 10, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel human pathological mutations. Gene symbol: GAA. Disease: glycogen storage disease 2.

Niu DM, Lin HY, Wu TJ, Hsu JH, Yu HC, Lin SP, Chuang CK, Huang CH.

Hum Genet. 2010 Apr;127(4):465. No abstract available.

PubMed [citation]

PMID:: 21488292

Clinical and GAA gene mutation analysis in mainland Chinese patients with late-onset Pompe disease: identifying c.2238G > C as the most common mutation.

Liu X, Wang Z, Jin W, Lv H, Zhang W, Que C, Huang Y, Yuan Y.

BMC Med Genet. 2014 Dec 20;15:141. doi: 10.1186/s12881-014-0141-2.

PubMed [citation]

PMID:: 25526786
PMCID:: PMC4411720

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001208300.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 168 of the GAA protein (p.Arg168Trp). This variant is present in population databases (rs777473001, gnomAD 0.004%). This missense change has been observed in individual(s) with Pompe disease (PMID: 30155607). ClinVar contains an entry for this variant (Variation ID: 842132). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg168 amino acid residue in GAA. Other variant(s) that disrupt this residue have been observed in individuals with GAA-related conditions (PMID: 21488292, 25526786, 30155607), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

From Genome-Nilou Lab, SCV002027216.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002091926.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002789176.1

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

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

Last Updated: Sep 29, 2024

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