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NM_000152.5(GAA):c.2105G>C (p.Arg702Pro) AND Glycogen storage disease, type II

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Mar 5, 2024
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:
RCV001585686.4

Allele description [Variation Report for NM_000152.5(GAA):c.2105G>C (p.Arg702Pro)]

NM_000152.5(GAA):c.2105G>C (p.Arg702Pro)

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.2105G>C (p.Arg702Pro)
Other names:
NM_000152.5(GAA):c.2105G>C; p.Arg702Pro
HGVS:
  • NC_000017.11:g.80113282G>C
  • NG_009822.1:g.16727G>C
  • NM_000152.5:c.2105G>CMANE SELECT
  • NM_001079803.3:c.2105G>C
  • NM_001079804.3:c.2105G>C
  • NP_000143.2:p.Arg702Pro
  • NP_001073271.1:p.Arg702Pro
  • NP_001073272.1:p.Arg702Pro
  • LRG_673:g.16727G>C
  • NC_000017.10:g.78087081G>C
  • NM_000152.4:c.2105G>C
Protein change:
R702P
Links:
dbSNP: rs398123172
NCBI 1000 Genomes Browser:
rs398123172
Molecular consequence:
  • NM_000152.5:c.2105G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079803.3:c.2105G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079804.3:c.2105G>C - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001810642Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jul 22, 2021) 		germlineclinical testing

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

SCV004227912ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel
reviewed by expert panel

(clingen_lsd_acmg_specifications_v2-1)		Uncertain significance
(Mar 5, 2024) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
not providedgermlinenonot providednot providednot providednot providednot providedclinical 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 Genome-Nilou Lab, SCV001810642.1

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

From ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel, SCV004227912.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000152.5:c.12105G>C variant in GAA is a missense variant predicted to cause substitution of arginine by proline at amino acid 702 (p.Arg702Pro). It has been reported in one individual in national mutation database for the country of Oman (PMID: 26594346). However, no clinical details were provided and thus points can not be applied for PP4. This individual was compound heterozygous for the variant and variant classified as pathogenic by the ClinGen LD VCEP (c.2560C>T, p.Arg854Ter; ClinVar Variation ID: Variation ID: 4034, SCV001371731.1), phase unknown (PMID: 26594346) (PM3_supporting). This variant is absent in gnomAD v2.1.1. (PM2_Supporting). The computational predictor REVEL gives a score of 0.989 which is above the threshold of 0.7, evidence that correlates with impact to GAA function (PP3). Another missense variant [c.2105G>T, p.Arg702Leu] in the same codon has been classified as pathogenic for Pompe disease by the ClinGen Lysosomal Diseases VCEP (ClinVar Variation ID: Variation ID: 92472) (PM5). There is a ClinVar entry for this variant (Variation ID: 593593). Due to insufficient evidence, this variant is classified as a variant of unknown significance for Pompe disease based on the GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (Specifications Version 2.0): (PM5, PM3_supporting, PM2_supporting, PP3). (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on March 5, 2024).

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

Last Updated: Apr 6, 2024