NM_000055.4(BCHE):c.635C>T (p.Ala212Val) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Aug 23, 2023
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002244851.7

Allele description [Variation Report for NM_000055.4(BCHE):c.635C>T (p.Ala212Val)]

NM_000055.4(BCHE):c.635C>T (p.Ala212Val)

Gene:

BCHE:butyrylcholinesterase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q26.1

Genomic location:

Preferred name:

NM_000055.4(BCHE):c.635C>T (p.Ala212Val)

HGVS:

NC_000003.12:g.165830399G>A
NG_009031.1:g.12067C>T
NM_000055.4:c.635C>TMANE SELECT
NP_000046.1:p.Ala212Val
NC_000003.11:g.165548187G>A
NM_000055.2:c.635C>T
NM_000055.3:c.635C>T
NR_137636.2:n.753C>T

Protein change:

A212V

Links:

dbSNP: rs114706984

NCBI 1000 Genomes Browser:

rs114706984

Molecular consequence:

NM_000055.4:c.635C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_137636.2:n.753C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002513661	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Apr 25, 2022)	germline	clinical testing	Citation Link,
SCV003800197	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Likely pathogenic (Aug 23, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002513661

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Apr 25, 2022)

germline

clinical testing

Citation Link,

SCV003800197

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Likely pathogenic
(Aug 23, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV002513661.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 18300943, 22750491, 20589221, 15731589, 7618741, 27109752)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV003800197.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The BCHE c.635C>T; p.Ala212Val variant, also published as Ala184Val, is reported in the literature as occurring in the homozygous state, compound heterozygous state, and heterozygous state, with at least two of the compound heterozygous individuals experiencing prolonged duration of succinylcholine action during routine anesthetic administration and reduced BChE activity (Greenberg 1995, Levano 2005, Mikami 2008). The variant is also listed in the ClinVar database (Variation ID: 370854), and is found in the general population with an overall allele frequency of 0.2% (595/281,610 alleles, including 1 homozygote) in the Genome Aggregation Database (v2.1.1). Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.365). Based on available information, the p.Ala212Val variant is classified as likely pathogenic. References: Greenberg CP et al. Prolonged response to succinylcholine: a new variant of plasma cholinesterase that is identified as normal by traditional phenotyping methods. Anesth Analg. 1995 Aug;81(2):419-21. PMID: 7618741. Levano S et al. Genotyping the butyrylcholinesterase in patients with prolonged neuromuscular block after succinylcholine. Anesthesiology. 2005 Mar;102(3):531-5. PMID: 15731589. Mikami LR et al. Five new naturally occurring mutations of the BCHE gene and frequencies of 12 butyrylcholinesterase alleles in a Brazilian population. Pharmacogenet Genomics. 2008 Mar;18(3):213-8. PMID: 18300943.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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