NM_000152.5(GAA):c.1216G>A (p.Asp406Asn) AND Glycogen storage disease, type II

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Nov 29, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000668100.3

Allele description [Variation Report for NM_000152.5(GAA):c.1216G>A (p.Asp406Asn)]

NM_000152.5(GAA):c.1216G>A (p.Asp406Asn)

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.1216G>A (p.Asp406Asn)

HGVS:

NC_000017.11:g.80108718G>A
NG_009822.1:g.12163G>A
NM_000152.5:c.1216G>AMANE SELECT
NM_001079803.3:c.1216G>A
NM_001079804.3:c.1216G>A
NP_000143.2:p.Asp406Asn
NP_001073271.1:p.Asp406Asn
NP_001073272.1:p.Asp406Asn
LRG_673t1:c.1216G>A
LRG_673:g.12163G>A
NC_000017.10:g.78082517G>A
NM_000152.3:c.1216G>A

Protein change:

D406N

Links:

dbSNP: rs1555600179

NCBI 1000 Genomes Browser:

rs1555600179

Molecular consequence:

NM_000152.5:c.1216G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001079803.3:c.1216G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001079804.3:c.1216G>A - 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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UGGT2 [Vulpes lagopus]
UGGT2 [Vulpes lagopus]
Gene ID:121477108

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000792650	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jul 5, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV004296864	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 29, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23430949, 31439017, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000792650

Counsyl

criteria provided, single submitter

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

Uncertain significance
(Jul 5, 2017)

unknown

clinical testing

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

Citation Link,

SCV004296864

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 29, 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

Newborn screening for lysosomal storage disorders in hungary.

Wittmann J, Karg E, Turi S, Legnini E, Wittmann G, Giese AK, Lukas J, Gölnitz U, Klingenhäger M, Bodamer O, Mühl A, Rolfs A.

JIMD Rep. 2012;6:117-25. doi: 10.1007/8904_2012_130. Epub 2012 Mar 21.

PubMed [citation]

PMID:: 23430949
PMCID:: PMC3565645

Comprehensive approach to weaning in difficult-to-wean infantile and juvenile-onset glycogen-storage disease type II patients: a case series.

Xu L, Ba H, Pei Y, Huang X, Liang Y, Zhang L, Huang H, Zhang C, Tang W.

Ital J Pediatr. 2019 Aug 22;45(1):106. doi: 10.1186/s13052-019-0692-0.

PubMed [citation]

PMID:: 31439017
PMCID:: PMC6704633

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000792650.1

#	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, SCV004296864.1

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GAA protein function. ClinVar contains an entry for this variant (Variation ID: 552776). This missense change has been observed in individual(s) with glycogen storage disease type II (PMID: 23430949, 31439017). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 406 of the GAA protein (p.Asp406Asn).

#	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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