NM_000152.5(GAA):c.2400C>T (p.Ser800=) AND not specified

Clinical significance:Benign/Likely benign (Last evaluated: Mar 11, 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:
RCV000153291.7

Allele description [Variation Report for NM_000152.5(GAA):c.2400C>T (p.Ser800=)]

NM_000152.5(GAA):c.2400C>T (p.Ser800=)

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.2400C>T (p.Ser800=)
HGVS:
  • NC_000017.11:g.80117668C>T
  • NG_009822.1:g.21113C>T
  • NM_000152.5:c.2400C>TMANE SELECT
  • NM_001079803.3:c.2400C>T
  • NM_001079804.3:c.2400C>T
  • NP_000143.2:p.Ser800=
  • NP_001073271.1:p.Ser800=
  • NP_001073272.1:p.Ser800=
  • LRG_673t1:c.2400C>T
  • LRG_673:g.21113C>T
  • LRG_673p1:p.(=)
  • NC_000017.10:g.78091467C>T
  • NM_000152.3:c.2400C>T
  • NM_000152.4:c.2400C>T
  • NP_000143.2:p.(=)
Links:
dbSNP: rs115705591
NCBI 1000 Genomes Browser:
rs115705591
Molecular consequence:
  • NM_000152.5:c.2400C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001079803.3:c.2400C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001079804.3:c.2400C>T - synonymous variant - [Sequence Ontology: SO:0001819]
Observations:
2

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000202768EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Benign
(Dec 13, 2013)
germlineclinical testing

Citation Link,

SCV000302679PreventionGenetics,PreventionGeneticscriteria provided, single submitter
Likely benigngermlineclinical testing

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

SCV000526400GeneDxcriteria provided, single submitter
Benign
(May 20, 2016)
germlineclinical testing

Citation Link,

SCV001361267Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Mar 11, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown2not providednot providednot providednot providedclinical testing
not providedgermlineyesnot 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 EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000202768.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided2not providednot providednot provided

From PreventionGenetics,PreventionGenetics, SCV000302679.1

#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, SCV000526400.4

#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, SCV001361267.1

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

Description

Variant summary: GAA c.2400C>T alters a non-conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: Four predict the variant creates a cryptic 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0023 in 275064 control chromosomes, predominantly at a frequency of 0.024 within the African subpopulation in the gnomAD database, including 8 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 6-folds higher than 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 African origin. To our knowledge, no occurrence of c.2400C>T in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite 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

Last Updated: Nov 27, 2021

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