NM_000152.5(GAA):c.236_246del (p.Pro79fs) AND Glycogen storage disease, type II

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Jun 16, 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:: RCV000409689.10

Allele description [Variation Report for NM_000152.5(GAA):c.236_246del (p.Pro79fs)]

NM_000152.5(GAA):c.236_246del (p.Pro79fs)

Gene:

GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.236_246del (p.Pro79fs)

HGVS:

NC_000017.11:g.80104822_80104832del
NG_009822.1:g.8267_8277del
NM_000152.5:c.236_246delMANE SELECT
NM_001079803.3:c.236_246del
NM_001079804.3:c.236_246del
NP_000143.2:p.Pro79fs
NP_001073271.1:p.Pro79fs
NP_001073272.1:p.Pro79fs
LRG_673t1:c.236_246del
LRG_673t1:c.236_246del11
LRG_673:g.8267_8277del
NC_000017.10:g.78078615_78078625del
NC_000017.10:g.78078621_78078631del
NM_000152.3:c.236_246del11
NM_000152.5(GAA):c.236_246delMANE SELECT
p.Pro79fs

Protein change:

P79fs

Links:

dbSNP: rs1057517165

NCBI 1000 Genomes Browser:

rs1057517165

Molecular consequence:

NM_000152.5:c.236_246del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079803.3:c.236_246del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079804.3:c.236_246del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000486851	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Pathogenic (Aug 23, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19588081, 17056254 mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV001443298	ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel	reviewed by expert panel (ClinGen LSD ACMG Specifications v1)	Pathogenic (Jun 16, 2020)	germline	curation	PubMed (12) [See all records that cite these PMIDs] 30371346, 17056254, 25998610, 29143201, 30022036, 22194990, 26913919, 19588081, 23825616, 30778879, 22980766, 32125626 Citation Link,
SCV003442414	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 22, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18425781, 22252923, 17056254, 28492532
SCV004195512	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 18, 2024)	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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Post-mortem diagnosis of Pompe disease by exome sequencing in a Moroccan family: a case report.

Adadi N, Sahli M, Egéa G, Ratbi I, Taoudi M, Zniber L, Jdioui W, El Mouatassim S, Sefiani A.

J Med Case Rep. 2018 Oct 29;12(1):322. doi: 10.1186/s13256-018-1855-0.

PubMed [citation]

PMID:: 30371346
PMCID:: PMC6205784

Targeted screening for the detection of Pompe disease in patients with unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using dried blood: A Spanish cohort.

Gutiérrez-Rivas E, Bautista J, Vílchez JJ, Muelas N, Díaz-Manera J, Illa I, Martínez-Arroyo A, Olivé M, Sanz I, Arpa J, Fernández-Torrón R, López de Munáin A, Jiménez L, Solera J, Lukacs Z.

Neuromuscul Disord. 2015 Jul;25(7):548-53. doi: 10.1016/j.nmd.2015.04.008. Epub 2015 Apr 23.

PubMed [citation]

PMID:: 25998610

See all PubMed Citations (16)

Details of each submission

From Counsyl, SCV000486851.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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

From ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel, SCV001443298.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (12)

Description

This variant, c.236_246del (p.Pro79ArgfsTer13), has been reported in multiple patients with Pompe disease. For two of these patients, residual GAA activity is reported and meets the ClinGen LSD VCEP's specifications for PP4 (PMID 17056254, 30778879). Both of these patients are compound heterozygous for the variant and a unique pathogenic variant; one with c.377G>A (p.Trp126Ter), in trans (PMID 17056254), and the other with c.1655T>C (p.Leu552Pro), phase unknown (PMID 30778879). This data meets PM3. Additional cases, both homozygous and compound heterozygous, have been reported but were not included because the residual GAA activity was not provided, and therefore PP4 cannot be assessed (PMIDs, 19588081, 22194990, 22980766, 23825616, 25998610, 26913919, 29143201, 30022036, 32125626). There is a ClinVar entry for this variant (Variation ID: 371302, 1 star review status) with 1 submitter classifying the variant as 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, PM3, PP4.

#	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, SCV003442414.2

#	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 creates a premature translational stop signal (p.Pro79Argfs*13) in the GAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Pompe disease (PMID: 17056254). ClinVar contains an entry for this variant (Variation ID: 371302). For these reasons, this variant has been classified as 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

From Baylor Genetics, SCV004195512.2

#	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

ClinVar

Relating variation to medicine