NM_000152.5(GAA):c.324T>C (p.Cys108=) AND Glycogen storage disease, type II

Germline classification:: Benign (7 submissions)
Last evaluated:: Jan 21, 2020
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000284275.20

Allele description [Variation Report for NM_000152.5(GAA):c.324T>C (p.Cys108=)]

NM_000152.5(GAA):c.324T>C (p.Cys108=)

Genes:

CCDC40:coiled-coil domain 40 molecular ruler complex subunit [Gene - OMIM - HGNC]
GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.324T>C (p.Cys108=)

HGVS:

NC_000017.11:g.80104910T>C
NG_009822.1:g.8355T>C
NM_000152.5:c.324T>CMANE SELECT
NM_001079803.3:c.324T>C
NM_001079804.3:c.324T>C
NP_000143.2:p.Cys108=
NP_001073271.1:p.Cys108=
NP_001073272.1:p.Cys108=
LRG_673t1:c.324T>C
LRG_673:g.8355T>C
NC_000017.10:g.78078709T>C
NM_000152.3:c.324T>C
NM_000152.4:c.324T>C
NM_000152.5(GAA):c.324T>CMANE SELECT
NM_001079803.1:c.324T>C
NM_001079804.1:c.324T>C
NP_000143.2:p.(=)
p.Cys108=
p.Cys108Cys

Links:

dbSNP: rs1800300

NCBI 1000 Genomes Browser:

rs1800300

Molecular consequence:

NM_000152.5:c.324T>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001079803.3:c.324T>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001079804.3:c.324T>C - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

Condition(s)

Name:: Glycogen storage disease, type II (GSD2)
Synonyms:: ACID ALPHA-GLUCOSIDASE DEFICIENCY; ALPHA-1,4-GLUCOSIDASE DEFICIENCY; CARDIOMEGALIA GLYCOGENICA DIFFUSA; 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
SCV000407257	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification 20161018)	Benign (Jun 14, 2016)	germline	clinical testing	ICSL_Variant_Classification_20161018.pdf, Citation Link,
SCV000679832	Phosphorus, Inc.	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Aug 1, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18414213, 23757202, 25741868
SCV000733721	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Benign	germline	clinical testing
SCV001371707	ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel	reviewed by expert panel (ClinGen LSD ACMG Specifications v1)	Benign (Jan 21, 2020)	germline	curation	Citation Link,
SCV001453582	Natera, Inc.	no assertion criteria provided	Benign (Sep 16, 2020)	germline	clinical testing
SCV001730023	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001738007	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jun 10, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	21	not provided	not provided	not provided	not provided	clinical testing, curation
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee.

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]

PMID:: 18414213

Free the data: one laboratory's approach to knowledge-based genomic variant classification and preparation for EMR integration of genomic data.

Bean LJ, Tinker SW, da Silva C, Hegde MR.

Hum Mutat. 2013 Sep;34(9):1183-8. doi: 10.1002/humu.22364. Epub 2013 Aug 5.

PubMed [citation]

PMID:: 23757202

See all PubMed Citations (4)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000407257.2

#	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 Phosphorus, Inc., SCV000679832.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	21	not provided	not provided	clinical testing	PubMed (3)

#	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		21	not provided	not provided	not provided

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV000733721.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel, SCV001371707.1

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

Description

The highest continental population minor allele frequency for c.324T>C (p.Cys108=) in gnomAD v2.1.1 is 0.81776 in the South Asian population. This is higher than the ClinGen LSD VCEP's BA1 threshold (>0.01), meeting this criterion. There is a ClinVar entry for this variant (Variation ID: 92484, two star review status), with 10 submitters classifying the variant as benign. In summary, this variant meets the criteria to be classified as benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: BA1.

#	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 Natera, Inc., SCV001453582.1

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001730023.4

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV001738007.1

#	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

Last Updated: Jan 13, 2025

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