NM_000152.5(GAA):c.2105G>C (p.Arg702Pro) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jul 1, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001193012.1

Allele description [Variation Report for NM_000152.5(GAA):c.2105G>C (p.Arg702Pro)]

NM_000152.5(GAA):c.2105G>C (p.Arg702Pro)

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.2105G>C (p.Arg702Pro)
HGVS:
  • NC_000017.11:g.80113282G>C
  • NG_009822.1:g.16727G>C
  • NM_000152.5:c.2105G>CMANE SELECT
  • NM_001079803.3:c.2105G>C
  • NM_001079804.3:c.2105G>C
  • NP_000143.2:p.Arg702Pro
  • NP_001073271.1:p.Arg702Pro
  • NP_001073272.1:p.Arg702Pro
  • LRG_673:g.16727G>C
  • NC_000017.10:g.78087081G>C
  • NM_000152.4:c.2105G>C
Protein change:
R702P
Links:
dbSNP: rs398123172
NCBI 1000 Genomes Browser:
rs398123172
Molecular consequence:
  • NM_000152.5:c.2105G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079803.3:c.2105G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079804.3:c.2105G>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001361536Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Jul 1, 2019)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Repository of mutations from Oman: The entry point to a national mutation database.

Rajab A, Hamza N, Al Harasi S, Al Lawati F, Gibbons U, Al Alawi I, Kobus K, Hassan S, Mahir G, Al Salmi Q, Mons B, Robinson P.

F1000Res. 2015;4:891. doi: 10.12688/f1000research.6938.1.

PubMed [citation]
PMID:
26594346
PMCID:
PMC4648203

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361536.1

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

Description

Variant summary: GAA c.2105G>C (p.Arg702Pro) affects a highly conserved nucleotide and results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 222484 control chromosomes (gnomAD). c.2105G>C has been reported in the literature in compound heterozygosity with a pathogenic GAA variant in an individual affected with Glycogen Storage Disease Type 2 (Pompe Disease), but limited information was provided on the case (Rajab_2015). These data therefore do not allow unequivocal conclusions about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, a variant affecting the same nucleotide but leading to a different missense change (c.2105G>A/p.Arg702His) has been classified by our laboratory as pathogenic. In addition, other variants affecting the same codon have been reported in affected individuals (c.2104C>T (p.Arg702Cys), c.2105G>T (p.Arg702Leu); in ClinVar and HGMD) suggesting a functional importance for this location. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Nov 27, 2021

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