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NM_000152.5(GAA):c.2780C>T (p.Thr927Ile) AND Glycogen storage disease, type II

Germline classification:
Benign (5 submissions)
Last evaluated:
Jan 23, 2020
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:
RCV000308857.25

Allele description [Variation Report for NM_000152.5(GAA):c.2780C>T (p.Thr927Ile)]

NM_000152.5(GAA):c.2780C>T (p.Thr927Ile)

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.2780C>T (p.Thr927Ile)
HGVS:
  • NC_000017.11:g.80118786C>T
  • NG_009822.1:g.22231C>T
  • NM_000152.4(GAA):c.2780C>T
  • NM_000152.5:c.2780C>TMANE SELECT
  • NM_001079803.3:c.2780C>T
  • NM_001079804.3:c.2780C>T
  • NP_000143.2:p.Thr927Ile
  • NP_000143.2:p.Thr927Ile
  • NP_001073271.1:p.Thr927Ile
  • NP_001073272.1:p.Thr927Ile
  • LRG_673t1:c.2780C>T
  • LRG_673:g.22231C>T
  • LRG_673p1:p.Thr927Ile
  • NC_000017.10:g.78092585C>T
  • NM_000152.3:c.2780C>T
  • NM_000152.4(GAA):c.2780C>T
  • NM_000152.4:c.2780C>T
  • P10253:p.Thr927Ile
Protein change:
T927I
Links:
UniProtKB: P10253#VAR_004317; dbSNP: rs1800315
NCBI 1000 Genomes Browser:
rs1800315
Molecular consequence:
  • NM_000152.5:c.2780C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079803.3:c.2780C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079804.3:c.2780C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV000407306Illumina Laboratory Services, Illumina
criteria provided, single submitter

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

Citation Link,

SCV000626601Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Benign
(Feb 1, 2024)
germlineclinical testing

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

SCV000679768Phosphorus, Inc.
criteria provided, single submitter

(ACMG Guidelines, 2015)
Benign
(Aug 1, 2017)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001371703ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel
reviewed by expert panel

(ClinGen LSD ACMG Specifications v1)
Benign
(Jan 23, 2020)
germlinecuration

Citation Link,

SCV001463867Natera, Inc.
no assertion criteria provided
Benign
(Sep 16, 2020)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing, curation

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

Mutation detection in glycogen storage-disease type II by RT-PCR and automated sequencing.

Hermans MM, van Leenen D, Kroos MA, Reuser AJ.

Biochem Biophys Res Commun. 1997 Dec 18;241(2):414-8.

PubMed [citation]
PMID:
9425285
See all PubMed Citations (6)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000407306.3

#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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000626601.6

#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 Phosphorus, Inc., SCV000679768.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel, SCV001371703.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The highest continental population minor allele frequency for c.2780C>T (p.Thr927Ile) in gnomAD v2.1.1 is 0.1317 in the African population. This is higher than the ClinGen LSD VCEP's BA1 threshold (>0.01), therefore meeting the BA1 criterion. There is a ClinVar entry for this variant (Variation ID: 92482; 2 star review status) with six submitters classifying the variant as benign, and two as likely benign. In summary, this variant meets the criteria to be classified as benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: BA1.

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

From Natera, Inc., SCV001463867.1

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

Last Updated: Oct 8, 2024