NM_000152.5(GAA):c.2332-12A>T AND Glycogen storage disease, type II

Clinical significance:Benign (Last evaluated: Oct 7, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001248964.2

Allele description [Variation Report for NM_000152.5(GAA):c.2332-12A>T]

NM_000152.5(GAA):c.2332-12A>T

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.2332-12A>T
HGVS:
  • NC_000017.11:g.80117588A>T
  • NG_009822.1:g.21033A>T
  • NM_000152.4(GAA):c.2332-12A>T
  • NM_000152.5:c.2332-12A>TMANE SELECT
  • NM_001079803.3:c.2332-12A>T
  • NM_001079804.3:c.2332-12A>T
  • LRG_673t1:c.2332-12A>T
  • LRG_673:g.21033A>T
  • NC_000017.10:g.78091387A>T
  • NM_000152.3:c.2332-12A>T
  • NM_000152.4(GAA):c.2332-12A>T
  • NM_000152.4:c.2332-12A>T
Links:
dbSNP: rs200965268
NCBI 1000 Genomes Browser:
rs200965268
Molecular consequence:
  • NM_000152.5:c.2332-12A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001079803.3:c.2332-12A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001079804.3:c.2332-12A>T - intron variant - [Sequence Ontology: SO:0001627]

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
SCV001422770Broad Institute Rare Disease Group, Broad Instituteno assertion criteria providedLikely benign
(Jan 22, 2020)
germlinecuration

Citation Link,

SCV001731834Invitaecriteria provided, single submitter
Benign
(Oct 7, 2020)
germlineclinical 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, 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Broad Institute Rare Disease Group, Broad Institute, SCV001422770.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.2332-12A>T variant in GAA has not been previously reported in individuals with Glycogen Storage Disease II but has been reported as a VUS by EGL Genetic Diagnostics and a likely benign variant by GeneDx and PreventionGenetics in ClinVar (Variation ID: 92475). This variant has been identified in 0.573% (142/24770) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs200965268). This variant has been seen in the general population at a greater frequency than expected for Glycogen Storage Disease II and is consistent with a benign role. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. However, novel synonymous variants supported by computational evidence without raised suspicion for an impact are likely benign (Richards 2015). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: BS1, BP4, BP7 (Richards 2015).

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

From Invitae, SCV001731834.1

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

Last Updated: Jun 23, 2021

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