NM_006567.5(FARS2):c.515TGG[2] (p.Val174del) AND Combined oxidative phosphorylation defect type 14

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 5, 2021
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:: RCV001341117.6

Allele description [Variation Report for NM_006567.5(FARS2):c.515TGG[2] (p.Val174del)]

NM_006567.5(FARS2):c.515TGG[2] (p.Val174del)

Genes:

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

Variant type:

Microsatellite

Cytogenetic location:

6p25.1

Genomic location:

Preferred name:

NM_006567.5(FARS2):c.515TGG[2] (p.Val174del)

HGVS:

NC_000006.12:g.5369085TGG[2]
NG_033003.2:g.112735TGG[2]
NM_001318872.2:c.515TGG[2]
NM_001374875.1:c.515TGG[2]
NM_001374876.1:c.515TGG[2]
NM_001374877.1:c.515TGG[2]
NM_001374878.1:c.515TGG[2]
NM_001374879.1:c.515TGG[2]
NM_001375257.1:c.515TGG[2]
NM_001375258.1:c.515TGG[2]
NM_001375259.1:c.-84-35457TGG[2]
NM_001375260.1:c.-340-27548TGG[2]
NM_006567.5:c.515TGG[2]MANE SELECT
NP_001305801.1:p.Val174del
NP_001361804.1:p.Val174del
NP_001361805.1:p.Val174del
NP_001361806.1:p.Val174del
NP_001361807.1:p.Val174del
NP_001361808.1:p.Val174del
NP_001362186.1:p.Val174del
NP_001362187.1:p.Val174del
NP_006558.1:p.Val174del
NC_000006.11:g.5369318TGG[2]
NC_000006.11:g.5369318_5369320del
NM_006567.4:c.521_523delTGG

Protein change:

V174del

Links:

OMIM: 611592.0010; dbSNP: rs1554169392

NCBI 1000 Genomes Browser:

rs1554169392

Molecular consequence:

NM_001318872.2:c.515TGG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001374875.1:c.515TGG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001374876.1:c.515TGG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001374877.1:c.515TGG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001374878.1:c.515TGG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001374879.1:c.515TGG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001375257.1:c.515TGG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001375258.1:c.515TGG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_006567.5:c.515TGG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001375259.1:c.-84-35457TGG[2] - intron variant - [Sequence Ontology: SO:0001627]
NM_001375260.1:c.-340-27548TGG[2] - intron variant - [Sequence Ontology: SO:0001627]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001534967	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 5, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29126765, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001534967

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 5, 2021)

germline

clinical testing

PubMed (2)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

New insights into the phenotype of FARS2 deficiency.

Vantroys E, Larson A, Friederich M, Knight K, Swanson MA, Powell CA, Smet J, Vergult S, De Paepe B, Seneca S, Roeyers H, Menten B, Minczuk M, Vanlander A, Van Hove J, Van Coster R.

Mol Genet Metab. 2017 Dec;122(4):172-181. doi: 10.1016/j.ymgme.2017.10.004. Epub 2017 Oct 12.

PubMed [citation]

PMID:: 29126765
PMCID:: PMC5734183

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001534967.4

#	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has been observed in individual(s) with clinical features of hereditary spastic paraplegia (PMID: 29126765). This variant is not present in population databases (ExAC no frequency). This variant, c.521_523del, results in the deletion of 1 amino acid(s) of the FARS2 protein (p.Val174del), but otherwise preserves the integrity of the reading frame.

#	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 20, 2024

ClinVar

Relating variation to medicine