NM_000152.5(GAA):c.1599C>T (p.Cys533=) AND Glycogen storage disease, type II

Clinical significance:Likely benign (Last evaluated: Jul 22, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV001088621.4

Allele description [Variation Report for NM_000152.5(GAA):c.1599C>T (p.Cys533=)]

NM_000152.5(GAA):c.1599C>T (p.Cys533=)

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.1599C>T (p.Cys533=)
HGVS:
  • NC_000017.11:g.80110988C>T
  • NG_009822.1:g.14433C>T
  • NM_000152.5:c.1599C>TMANE SELECT
  • NM_001079803.3:c.1599C>T
  • NM_001079804.3:c.1599C>T
  • NP_000143.2:p.Cys533=
  • NP_001073271.1:p.Cys533=
  • NP_001073272.1:p.Cys533=
  • LRG_673t1:c.1599C>T
  • LRG_673:g.14433C>T
  • NC_000017.10:g.78084787C>T
  • NM_000152.3:c.1599C>T
  • NM_000152.4(GAA):c.1599C>T
  • p.Cys533=
Links:
dbSNP: rs142766716
NCBI 1000 Genomes Browser:
rs142766716
Molecular consequence:
  • NM_000152.5:c.1599C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001079803.3:c.1599C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001079804.3:c.1599C>T - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV000626521Invitaecriteria provided, single submitter
Likely benign
(Nov 11, 2020)
germlineclinical testing

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

SCV001422774Broad Institute Rare Disease Group, Broad Instituteno assertion criteria providedLikely benign
(Jan 22, 2020)
germlinecuration

Citation Link,

SCV001810616Nilou-Genome Labcriteria provided, single submitter
Likely benign
(Jul 22, 2021)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
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

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 Invitae, SCV000626521.4

#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 Broad Institute Rare Disease Group, Broad Institute, SCV001422774.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.1599C>T (p.Cys533=) 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 Invitae and PreventionGenetics in ClinVar (Variation ID: 255354). This variant has been identified in 0.080% (20/24944) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs142766716). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. 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: PM2, BP4, BP7 (Richards 2015).

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

From Nilou-Genome Lab, SCV001810616.1

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

Last Updated: Nov 27, 2021

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