NM_000152.5(GAA):c.2261dup (p.Val755fs) AND Glycogen storage disease, type II

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 18, 2023
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:: RCV001810324.2

Allele description [Variation Report for NM_000152.5(GAA):c.2261dup (p.Val755fs)]

NM_000152.5(GAA):c.2261dup (p.Val755fs)

Gene:

GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.2261dup (p.Val755fs)

HGVS:

NC_000017.11:g.80117039dup
NG_009822.1:g.20484dup
NM_000152.5:c.2261dupMANE SELECT
NM_001079803.3:c.2261dup
NM_001079804.3:c.2261dup
NP_000143.2:p.Val755fs
NP_001073271.1:p.Val755fs
NP_001073272.1:p.Val755fs
LRG_673t1:c.2261dup
LRG_673:g.20484dup
NC_000017.10:g.78090838dup
NM_000152.3:c.2261dup

Protein change:

V755fs

Links:

dbSNP: rs1555602648

NCBI 1000 Genomes Browser:

rs1555602648

Molecular consequence:

NM_000152.5:c.2261dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079803.3:c.2261dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079804.3:c.2261dup - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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
SCV002058864	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 3, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] PMID:31342611,
SCV004195443	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 18, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002058864

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 3, 2022)

germline

clinical testing

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

PMID:31342611,

SCV004195443

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 18, 2023)

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	yes	1	not provided	not provided	1	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

Details of each submission

From 3billion, SCV002058864.1

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

Description

Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant has been reported to be associated with GAA related disorder (PMID:31342611). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

From Baylor Genetics, SCV004195443.1

#	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: Mar 16, 2024

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