NM_021957.4(GYS2):c.1745G>A (p.Arg582Lys) AND Glycogen storage disease due to hepatic glycogen synthase deficiency

Clinical significance:Uncertain significance (Last evaluated: Nov 2, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000642238.1

Allele description [Variation Report for NM_021957.4(GYS2):c.1745G>A (p.Arg582Lys)]

NM_021957.4(GYS2):c.1745G>A (p.Arg582Lys)

Gene:
GYS2:glycogen synthase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12p12.1
Genomic location:
Preferred name:
NM_021957.4(GYS2):c.1745G>A (p.Arg582Lys)
HGVS:
  • NC_000012.12:g.21540474C>T
  • NG_016167.1:g.69374G>A
  • NM_021957.4:c.1745G>AMANE SELECT
  • NP_068776.2:p.Arg582Lys
  • LRG_1293t1:c.1745G>A
  • LRG_1293:g.69374G>A
  • LRG_1293p1:p.Arg582Lys
  • NC_000012.11:g.21693408C>T
  • NM_021957.3:c.1745G>A
Protein change:
R582K
Links:
dbSNP: rs369069984
NCBI 1000 Genomes Browser:
rs369069984
Molecular consequence:
  • NM_021957.4:c.1745G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Glycogen storage disease due to hepatic glycogen synthase deficiency (GSD0A)
Synonyms:
GSD 0a; LIVER GLYCOGEN SYNTHASE DEFICIENCY; Hypoglycemia with deficiency of glycogen synthetase in the liver
Identifiers:
MONDO: MONDO:0009414; MedGen: C1855861; Orphanet: 2089; OMIM: 240600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000763894Invitaecriteria provided, single submitter
Uncertain significance
(Nov 2, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in children.

Brown LM, Corrado MM, van der Ende RM, Derks TG, Chen MA, Siegel S, Hoyt K, Correia CE, Lumpkin C, Flanagan TB, Carreras CT, Weinstein DA.

J Inherit Metab Dis. 2015 May;38(3):489-93. doi: 10.1007/s10545-014-9744-1. Epub 2014 Jul 29.

PubMed [citation]
PMID:
25070466

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 Invitae, SCV000763894.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces arginine with lysine at codon 582 of the GYS2 protein (p.Arg582Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant is present in population databases (rs369069984, ExAC 0.004%). This variant has been reported in an individual affected with glycogen storage disease (PMID: 25070466). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 27, 2021

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