NM_001358921.2(COQ2):c.232A>G (p.Met78Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 15, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001853076.13

Allele description [Variation Report for NM_001358921.2(COQ2):c.232A>G (p.Met78Val)]

NM_001358921.2(COQ2):c.232A>G (p.Met78Val)

Genes:

LOC112997540:Sharpr-MPRA regulatory region 13773 [Gene]
COQ2:coenzyme Q2, polyprenyltransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q21.23

Genomic location:

Preferred name:

NM_001358921.2(COQ2):c.232A>G (p.Met78Val)

Other names:

232A>G

HGVS:

NC_000004.12:g.83284533T>C
NG_015825.1:g.5382A>G
NM_001358921.2:c.232A>GMANE SELECT
NM_015697.9:c.382A>G
NP_001345850.1:p.Met78Val
NP_056512.5:p.Met128Val
NC_000004.11:g.84205686T>C
NM_015697.7:c.382A>G
NM_015697.8:c.382A>G

Protein change:

M128V; MET128VAL

Links:

OMIM: 609825.0006; dbSNP: rs778094136

NCBI 1000 Genomes Browser:

rs778094136

Molecular consequence:

NM_001358921.2:c.232A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_015697.9:c.382A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002176239	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 15, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23758206, 28492532
SCV005190155	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	germline	not provided	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002176239

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 15, 2022)

germline

clinical testing

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

SCV005190155

Breakthrough Genomics, Breakthrough Genomics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

germline

not provided

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

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	not provided
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in COQ2 in familial and sporadic multiple-system atrophy.

Multiple-System Atrophy Research Collaboration.

N Engl J Med. 2013 Jul 18;369(3):233-44. doi: 10.1056/NEJMoa1212115. Epub 2013 Jun 12. Erratum in: N Engl J Med. 2014 Jul 3;371(1):94.

PubMed [citation]

PMID:: 23758206

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002176239.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. Experimental studies have shown that this missense change affects COQ2 function (PMID: 23758206). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COQ2 protein function. ClinVar contains an entry for this variant (Variation ID: 60536). This missense change has been observed in individual(s) with multiple system atrophy (PMID: 23758206). This variant is present in population databases (rs778094136, gnomAD 0.07%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 128 of the COQ2 protein (p.Met128Val).

#	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

From Breakthrough Genomics, Breakthrough Genomics, SCV005190155.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	PubMed (1)

#	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

Last Updated: Jan 26, 2025

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