NM_006567.5(FARS2):c.442C>T (p.Arg148Trp) AND Combined oxidative phosphorylation defect type 14

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 25, 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:: RCV003873348.2

Allele description [Variation Report for NM_006567.5(FARS2):c.442C>T (p.Arg148Trp)]

NM_006567.5(FARS2):c.442C>T (p.Arg148Trp)

Genes:

LOC126859565:CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:5368745-5369944 [Gene]
FARS2:phenylalanyl-tRNA synthetase 2, mitochondrial [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p25.1

Genomic location:

Preferred name:

NM_006567.5(FARS2):c.442C>T (p.Arg148Trp)

HGVS:

NC_000006.12:g.5369012C>T
NG_033003.2:g.112662C>T
NG_033003.3:g.124080C>T
NG_084066.2:g.937C>T
NM_001318872.2:c.442C>T
NM_001374875.1:c.442C>T
NM_001374876.1:c.442C>T
NM_001374877.1:c.442C>T
NM_001374878.1:c.442C>T
NM_001374879.1:c.442C>T
NM_001375257.1:c.442C>T
NM_001375258.1:c.442C>T
NM_001375259.1:c.-84-35530C>T
NM_001375260.1:c.-340-27621C>T
NM_006567.5:c.442C>TMANE SELECT
NP_001305801.1:p.Arg148Trp
NP_001361804.1:p.Arg148Trp
NP_001361805.1:p.Arg148Trp
NP_001361806.1:p.Arg148Trp
NP_001361807.1:p.Arg148Trp
NP_001361808.1:p.Arg148Trp
NP_001362186.1:p.Arg148Trp
NP_001362187.1:p.Arg148Trp
NP_006558.1:p.Arg148Trp
NC_000006.11:g.5369245C>T

Protein change:

R148W

Molecular consequence:

NM_001375259.1:c.-84-35530C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001375260.1:c.-340-27621C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001318872.2:c.442C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374875.1:c.442C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374876.1:c.442C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374877.1:c.442C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374878.1:c.442C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374879.1:c.442C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375257.1:c.442C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375258.1:c.442C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006567.5:c.442C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Combined oxidative phosphorylation defect type 14
Synonyms:: Combined oxidative phosphorylation deficiency 14
Identifiers:: MONDO: MONDO:0013986; MedGen: C4755312; Orphanet: 319519; OMIM: 614946

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004676527	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 25, 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

SCV004676527

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 25, 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004676527.1

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

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 148 of the FARS2 protein (p.Arg148Trp). 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. 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 expected to disrupt FARS2 protein function. This variant has not been reported in the literature in individuals affected with FARS2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%).

#	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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