NM_000055.2(BCHE):c.293A>G (p.Asp98Gly) AND Deficiency of butyrylcholine esterase

Clinical significance:Pathogenic (Last evaluated: Jun 14, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000277104.1

Allele description

NM_000055.2(BCHE):c.293A>G (p.Asp98Gly)

Gene:
BCHE:butyrylcholinesterase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q26.1
Genomic location:
Preferred name:
NM_000055.2(BCHE):c.293A>G (p.Asp98Gly)
Other names:
BCHE*70G; A-Variant
HGVS:
  • NC_000003.12:g.165830741T>C
  • NG_009031.1:g.11725A>G
  • NM_000055.3:c.293A>G
  • NP_000046.1:p.Asp98Gly
  • NC_000003.11:g.165548529T>C
  • NM_000055.2:c.293A>G
  • NR_137635.1:n.159+6573A>G
  • NR_137636.1:n.460A>G
  • P06276:p.Asp98Gly
Protein change:
D70G; ASP70GLY
Links:
UniProtKB: P06276#VAR_002360; OMIM: 177400.0001; dbSNP: rs1799807
GMAF:
0.0060(C), 1799807
NCBI 1000 Genomes Browser:
rs1799807
Allele Frequency:
0.01207(C), GO-ESP
Molecular consequence:
  • NR_137635.1:n.159+6573A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000055.3:c.293A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_137636.1:n.460A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Deficiency of butyrylcholine esterase
Synonyms:
BCHE, silent 1; Succinylcholine response; Mivacurium response
Identifiers:
MedGen: C1283400; OMIM: 177400

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000442044Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Pathogenic
(Jun 14, 2016)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

ICSL_Variant_Classification_20161018.pdf

Citation Link

Summary from all submissions

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

Citations

PubMed

Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase.

McGuire MC, Nogueira CP, Bartels CF, Lightstone H, Hajra A, Van der Spek AF, Lockridge O, La Du BN.

Proc Natl Acad Sci U S A. 1989 Feb;86(3):953-7.

PubMed [citation]
PMID:
2915989
PMCID:
PMC286597

A method for the detection of atypical forms of human serum cholinesterase; determination of dibucaine numbers.

KALOW W, GENEST K.

Can J Biochem Physiol. 1957 Jun;35(6):339-46. No abstract available.

PubMed [citation]
PMID:
13437188
See all PubMed Citations (4)

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000442044.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The c.293A>G (p.Asp98Gly) variant is well-described in the literature, more commonly referred to as p.Asp70Gly, BCHE*A, BCHE*70G or CHE*70G. Homozygosity for this variant causes the atypical butyrylcholinesterase (BCHE) deficiency phenotype, first described by Kalow (1957). McGuire et al. (1989) studied 26 individuals with the atypical phenotype, including 15 individuals from a large three-generation family. They found complete concordance between the p.Asp98Gly variant and serum cholinesterase phenotypes for all atypical subjects tested. Yen et al. (2003) genotyped 52 patients in Australia with post-succinylcholine (SC) apnea attributable to BCHE variants. The p.Asp98Gly variant (A allele) was found in 47/52 patients with an allele frequency of 0.72. Co-inheritance of the A allele and another well-described variant, p.Aka567Thr (the K allele) occurred in 88% of patients. Twenty-three patients were homozygous for both the A allele and the K allele (AAKK), the most common genotype. In addition seven patients were compound heterozygotes for the A allele and the K allele (AK), four were homozygous for the A allele and heterozygous for the K allele (AAK), four were heterozygous for the A allele and homozygous for the K allele (AKK) and nine had compound genotypes with other variants in the BCHE gene. Their study indicated that compound genotypes are most often associated with post-succinylcholine (SC) apnea. In a review by Lockridge et al (2015), the p.Asp98Gly variant is reported to have 50% enzyme activity, to reduce the binding affinity for succinylcholine 100-fold and to have a carrier frequency of 1/25. This agrees with the highest reported allele frequency of 0.03738 in the Toscani in Italy population of the 1000 Genomes Project, confirming that this is a common variant. Based on the collective evidence, the p.Asp98Gly variant is classified as pathogenic for butyrylcholinesterase deficiency.

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

Last Updated: Sep 5, 2017

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