NM_001358921.2(COQ2):c.368G>A (p.Arg123His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 29, 2024
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:: RCV001837084.4

Allele description [Variation Report for NM_001358921.2(COQ2):c.368G>A (p.Arg123His)]

NM_001358921.2(COQ2):c.368G>A (p.Arg123His)

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.368G>A (p.Arg123His)

HGVS:

NC_000004.12:g.83279000C>T
NG_015825.1:g.10915G>A
NM_001358921.2:c.368G>AMANE SELECT
NM_015697.9:c.518G>A
NP_001345850.1:p.Arg123His
NP_056512.5:p.Arg173His
NC_000004.11:g.84200153C>T
NM_015697.7:c.518G>A
NM_015697.8:c.518G>A

Protein change:

R123H

Links:

dbSNP: rs752363398

NCBI 1000 Genomes Browser:

rs752363398

Molecular consequence:

NM_001358921.2:c.368G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015697.9:c.518G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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NP_776590 (0)
GEO DataSets
PREDICTED: Brassica rapa uncharacterized LOC103844700 (LOC103844700), mRNA
PREDICTED: Brassica rapa uncharacterized LOC103844700 (LOC103844700), mRNA
gi|1827943131|ref|XM_009121514.3|

Nucleotide
cytochrome c oxidase subunit I, partial (mitochondrion) [Halicreatidae sp.]
cytochrome c oxidase subunit I, partial (mitochondrion) [Halicreatidae sp.]
gi|2689170483|gb|WWP50992.1|

Protein
cytochrome c oxidase subunit I, partial (mitochondrion) [Limnocnida indica]
cytochrome c oxidase subunit I, partial (mitochondrion) [Limnocnida indica]
gi|2734690946|gb|XAX87717.1|

Protein
Lepas anatifera isolate LESH14 cytochrome c oxidase subunit I (COX1) gene, parti...
Lepas anatifera isolate LESH14 cytochrome c oxidase subunit I (COX1) gene, partial cds; mitochondrial
gi|2500952291|gb|OQ933560.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002097437	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Feb 29, 2024)	germline	clinical testing	Citation Link,
SCV003282559	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 12, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30180404, 32604935, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002097437

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Feb 29, 2024)

germline

clinical testing

Citation Link,

SCV003282559

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 12, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Citations

PubMed

[Clinical analysis of one infantile nephrotic syndrome caused by COQ2 gene mutation and literature review].

Xu K, Mao XY, Yao Y, Cheng H, Zhang XJ.

Zhonghua Er Ke Za Zhi. 2018 Sep 2;56(9):662-666. doi: 10.3760/cma.j.issn.0578-1310.2018.09.006. Review. Chinese.

PubMed [citation]

PMID:: 30180404

Genetic Study in Korean Pediatric Patients with Steroid-Resistant Nephrotic Syndrome or Focal Segmental Glomerulosclerosis.

Park E, Lee C, Kim NKD, Ahn YH, Park YS, Lee JH, Kim SH, Cho MH, Cho H, Yoo KH, Shin JI, Kang HG, Ha IS, Park WY, Cheong HI.

J Clin Med. 2020 Jun 26;9(6). doi:pii: E2013. 10.3390/jcm9062013. Erratum in: J Clin Med. 2022 May 27;11(11):3016. doi: 10.3390/jcm11113016.

PubMed [citation]

PMID:: 32604935
PMCID:: PMC7355646

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV002097437.3

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

Description

Identified in individuals with focal segmental glomerulosclerosis who harbored a second COQ2 variant, but it is unknown if the variants were on the same (in cis) or opposite (in trans) COQ2 alleles (PMID: 25349199, 35683636, 35483523); Identified in the heterozygous state in unrelated adult individuals with ataxia and other Parkinsonism features (PMID: 26096180, 25442117); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30030365, 30180404, 32604935, 34426522, 36420660, 25349199, 35683636, 36982356, 36765380, 35483523, 26096180, 35112026, 25442117)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003282559.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 173 of the COQ2 protein (p.Arg173His). This variant is present in population databases (rs752363398, gnomAD 0.1%). This missense change has been observed in individual(s) with clinical features of coenzyme Q10 deficiency (PMID: 30180404, 32604935). ClinVar contains an entry for this variant (Variation ID: 1341588). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.

#	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: Oct 8, 2024

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