NM_024537.4(CARS2):c.851_852delinsGG (p.Glu284Gly) AND Combined oxidative phosphorylation defect type 27

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 5, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000798921.4

Allele description [Variation Report for NM_024537.4(CARS2):c.851_852delinsGG (p.Glu284Gly)]

NM_024537.4(CARS2):c.851_852delinsGG (p.Glu284Gly)

Gene:

CARS2:cysteinyl-tRNA synthetase 2, mitochondrial [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

13q34

Genomic location:

Preferred name:

NM_024537.4(CARS2):c.851_852delinsGG (p.Glu284Gly)

HGVS:

NC_000013.11:g.110667407_110667408delinsCC
NG_042045.2:g.51194_51195delinsGG
NM_001352252.2:c.65_66delinsGG
NM_001352253.3:c.851_852delinsGG
NM_024537.4:c.851_852delinsGGMANE SELECT
NP_001339181.1:p.Glu22Gly
NP_001339182.1:p.Glu284Gly
NP_078813.1:p.Glu284Gly
NC_000013.10:g.111319754_111319755delinsCC
NM_024537.3:c.851_852delAAinsGG
NR_147941.1:n.822_823delinsGG
NR_147942.2:n.874_875delinsGG

Protein change:

E22G

Links:

dbSNP: rs1594296703

NCBI 1000 Genomes Browser:

rs1594296703

Molecular consequence:

NM_001352252.2:c.65_66delinsGG - missense variant - [Sequence Ontology: SO:0001583]
NM_001352253.3:c.851_852delinsGG - missense variant - [Sequence Ontology: SO:0001583]
NM_024537.4:c.851_852delinsGG - missense variant - [Sequence Ontology: SO:0001583]
NR_147941.1:n.822_823delinsGG - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147942.2:n.874_875delinsGG - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Combined oxidative phosphorylation defect type 27
Synonyms:: Combined oxidative phosphorylation deficiency 27
Identifiers:: MONDO: MONDO:0014728; MedGen: C5567608; OMIM: 616672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000938564	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 5, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000938564

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 5, 2022)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000938564.4

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

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 644921). This variant has not been reported in the literature in individuals affected with CARS2-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces glutamic acid with glycine at codon 284 of the CARS2 protein (p.Glu284Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine.

#	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: Feb 14, 2024

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