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NM_000152.5(GAA):c.1726G>A (p.Gly576Ser) AND Glycogen storage disease, type II

Germline classification:
Conflicting interpretations of pathogenicity; other (6 submissions)
Last evaluated:
Mar 30, 2024
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:
RCV000353996.32

Allele description [Variation Report for NM_000152.5(GAA):c.1726G>A (p.Gly576Ser)]

NM_000152.5(GAA):c.1726G>A (p.Gly576Ser)

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.1726G>A (p.Gly576Ser)
HGVS:
  • NC_000017.11:g.80112072G>A
  • NG_009822.1:g.15517G>A
  • NM_000152.5:c.1726G>AMANE SELECT
  • NM_001079803.3:c.1726G>A
  • NM_001079804.3:c.1726G>A
  • NP_000143.2:p.Gly576Ser
  • NP_000143.2:p.Gly576Ser
  • NP_001073271.1:p.Gly576Ser
  • NP_001073272.1:p.Gly576Ser
  • LRG_673t1:c.1726G>A
  • LRG_673:g.15517G>A
  • LRG_673p1:p.Gly576Ser
  • NC_000017.10:g.78085871G>A
  • NM_000152.3:c.1726G>A
  • P10253:p.Gly576Ser
Protein change:
G576S
Links:
UniProtKB: P10253#VAR_004300; dbSNP: rs1800307
NCBI 1000 Genomes Browser:
rs1800307
Molecular consequence:
  • NM_000152.5:c.1726G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079803.3:c.1726G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079804.3:c.1726G>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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000407284Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)
Benign
(Mar 6, 2018)
germlineclinical testing

Citation Link,

SCV000626522Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
other
(Dec 31, 2018)
germlineclinical testing

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

SCV001158935ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)
Benign
(Oct 26, 2023)
germlineclinical testing

Citation Link,

SCV001749549GenomeConnect - Invitae Patient Insights Network
no classification provided
not providedunknownphenotyping only

SCV001761182GeneReviews
no classification provided
not providedgermlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

SCV004195413Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Mar 30, 2024)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, literature only
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing, phenotyping only

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Genetic heterozygosity and pseudodeficiency in the Pompe disease newborn screening pilot program.

Labrousse P, Chien YH, Pomponio RJ, Keutzer J, Lee NC, Akmaev VR, Scholl T, Hwu WL.

Mol Genet Metab. 2010 Apr;99(4):379-83. doi: 10.1016/j.ymgme.2009.12.014. Epub 2009 Dec 28.

PubMed [citation]
PMID:
20080426
See all PubMed Citations (6)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000407284.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000626522.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001158935.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GenomeConnect - Invitae Patient Insights Network, SCV001749549.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedphenotyping onlynot provided

Description

Variant interpreted as Benign and reported on 03-18-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneReviews, SCV001761182.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (4)

Description

Pseudodeficiency allele c.1726 G>A (p.Gly576Ser), which interferes with enzyme activity toward artificial substrates, is relatively common in Asian as well as other populations studied as part of newborn screening programs.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV004195413.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2024