NM_000152.5(GAA):c.852G>A (p.Ala284=) AND not specified

Clinical significance:Benign (Last evaluated: Apr 22, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000168659.8

Allele description [Variation Report for NM_000152.5(GAA):c.852G>A (p.Ala284=)]

NM_000152.5(GAA):c.852G>A (p.Ala284=)

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.852G>A (p.Ala284=)
HGVS:
  • NC_000017.11:g.80107716G>A
  • NG_009822.1:g.11161G>A
  • NM_000152.5:c.852G>AMANE SELECT
  • NM_001079803.3:c.852G>A
  • NM_001079804.3:c.852G>A
  • NP_000143.2:p.Ala284=
  • NP_001073271.1:p.Ala284=
  • NP_001073272.1:p.Ala284=
  • LRG_673t1:c.852G>A
  • LRG_673:g.11161G>A
  • NC_000017.10:g.78081515G>A
  • NM_000152.3:c.852G>A
  • NM_000152.4:c.852G>A
  • NM_000152.5(GAA):c.852G>AMANE SELECT
  • p.Ala284=
  • p.Ala284Ala
Links:
dbSNP: rs142626724
NCBI 1000 Genomes Browser:
rs142626724
Molecular consequence:
  • NM_000152.5:c.852G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001079803.3:c.852G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001079804.3:c.852G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000302697PreventionGenetics,PreventionGeneticscriteria provided, single submitter
Benigngermlineclinical testing

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

SCV000518529GeneDxcriteria provided, single submitter
Benign
(Dec 22, 2015)
germlineclinical testing

Citation Link,

SCV001363613Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Apr 22, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV001974663Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedBenigngermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot 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

Glycogen storage disease type II in Spanish patients: high frequency of c.1076-1G>C mutation.

Gort L, Coll MJ, Chabás A.

Mol Genet Metab. 2007 Sep-Oct;92(1-2):183-7. Epub 2007 Jul 5.

PubMed [citation]
PMID:
17616415
See all PubMed Citations (4)

Details of each submission

From PreventionGenetics,PreventionGenetics, SCV000302697.1

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

From GeneDx, SCV000518529.4

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363613.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: GAA c.852G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0063 in 248578 control chromosomes, predominantly at a frequency of 0.01 within the Non-Finnish European subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) phenotype (0.0042), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. The variant, c.852G>A has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) without strong evidence of causality (Gort_2007, Herzog_2012, Kroos_2008) . These reports do not provide unequivocal conclusions about association of the variant with Glycogen Storage Disease, Type 2 (Pompe Disease). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001974663.1

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

Last Updated: Nov 10, 2021

Support Center