NM_000152.5(GAA):c.711_712dup (p.Pro238fs) AND Glycogen storage disease, type II

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 6, 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:: RCV000674654.4

Allele description [Variation Report for NM_000152.5(GAA):c.711_712dup (p.Pro238fs)]

NM_000152.5(GAA):c.711_712dup (p.Pro238fs)

Gene:

GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.711_712dup (p.Pro238fs)

HGVS:

NC_000017.11:g.80107573GC[3]
NG_009822.1:g.11018GC[3]
NM_000152.5:c.711_712dupMANE SELECT
NM_001079803.3:c.711_712dup
NM_001079804.3:c.711_712dup
NP_000143.2:p.Pro238fs
NP_001073271.1:p.Pro238fs
NP_001073272.1:p.Pro238fs
LRG_673:g.11018GC[3]
NC_000017.10:g.78081371_78081372insGC
NC_000017.10:g.78081372GC[3]

Protein change:

P238fs

Links:

dbSNP: rs1555599586

NCBI 1000 Genomes Browser:

rs1555599586

Molecular consequence:

NM_000152.5:c.711_712dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079803.3:c.711_712dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079804.3:c.711_712dup - 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

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Homo sapiens KIAA0480 gene product (KIAA0480), mRNA
Homo sapiens KIAA0480 gene product (KIAA0480), mRNA
gi|7662155|ref|NM_014810.1|

Nucleotide
Homologene neighbors for GEO Profiles (Select 121671406) (0)
GEO Profiles
Sotrastaurin effect on mantle cell lymphoma cell lines
Sotrastaurin effect on mantle cell lymphoma cell lines
Accession: GDS5309

GEO DataSets
Related DataSets for GEO Profiles (Select 121671815) (1)
GEO DataSets

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000800029	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (May 21, 2018)	unknown	clinical testing	Citation Link,
SCV002796810	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 12, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004667005	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 6, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18425781, 22252923, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000800029

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(May 21, 2018)

unknown

clinical testing

Citation Link,

SCV002796810

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 12, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004667005

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 6, 2022)

germline

clinical testing

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

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating.

Kroos M, Pomponio RJ, van Vliet L, Palmer RE, Phipps M, Van der Helm R, Halley D, Reuser A; GAA Database Consortium..

Hum Mutat. 2008 Jun;29(6):E13-26. doi: 10.1002/humu.20745.

PubMed [citation]

PMID:: 18425781

See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000800029.1

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

From Fulgent Genetics, Fulgent Genetics, SCV002796810.1

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004667005.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with GAA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro238Argfs*31) 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).

#	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: Sep 29, 2024

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