NM_021957.4(GYS2):c.1672C>T (p.Arg558Cys) AND Glycogen storage disease due to hepatic glycogen synthase deficiency

Clinical significance:Uncertain significance (Last evaluated: Sep 24, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000803417.1

Allele description [Variation Report for NM_021957.4(GYS2):c.1672C>T (p.Arg558Cys)]

NM_021957.4(GYS2):c.1672C>T (p.Arg558Cys)

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.1672C>T (p.Arg558Cys)
HGVS:
  • NC_000012.12:g.21540547G>A
  • NG_016167.1:g.69301C>T
  • NM_021957.4:c.1672C>TMANE SELECT
  • NP_068776.2:p.Arg558Cys
  • LRG_1293t1:c.1672C>T
  • LRG_1293:g.69301C>T
  • LRG_1293p1:p.Arg558Cys
  • NC_000012.11:g.21693481G>A
  • NM_021957.3:c.1672C>T
Protein change:
R558C
Links:
dbSNP: rs148617918
NCBI 1000 Genomes Browser:
rs148617918
Molecular consequence:
  • NM_021957.4:c.1672C>T - 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
SCV000943288Invitaecriteria provided, single submitter
Uncertain significance
(Sep 24, 2018)
germlineclinical testing

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

Summary from all submissions

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

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

Details of each submission

From Invitae, SCV000943288.1

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

Description

This sequence change replaces arginine with cysteine at codon 558 of the GYS2 protein (p.Arg558Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs148617918, ExAC 0.03%). This variant has not been reported in the literature in individuals with GYS2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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