NM_006567.5(FARS2):c.1255C>T (p.Arg419Cys) AND Combined oxidative phosphorylation deficiency 14

Clinical significance:Likely pathogenic (Last evaluated: Mar 11, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001378476.1

Allele description [Variation Report for NM_006567.5(FARS2):c.1255C>T (p.Arg419Cys)]

NM_006567.5(FARS2):c.1255C>T (p.Arg419Cys)

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.1255C>T (p.Arg419Cys)
Other names:
p.R419C:CGC>TGC
HGVS:
  • NC_000006.12:g.5771328C>T
  • NG_033003.1:g.514978C>T
  • NG_033003.2:g.514978C>T
  • NM_001318872.1:c.1255C>T
  • NM_006567.5:c.1255C>TMANE SELECT
  • NP_001305801.1:p.Arg419Cys
  • NP_006558.1:p.Arg419Cys
  • NC_000006.11:g.5771561C>T
  • NM_006567.3:c.1255C>T
  • NM_006567.4:c.1255C>T
Protein change:
R419C; ARG419CYS
Links:
OMIM: 611592.0006; dbSNP: rs775690041
NCBI 1000 Genomes Browser:
rs775690041
Molecular consequence:
  • NM_001318872.1:c.1255C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006567.5:c.1255C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Combined oxidative phosphorylation deficiency 14 (COXPD14)
Identifiers:
MONDO: MONDO:0013986; MedGen: C3554168; Orphanet: 319519; OMIM: 614946

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001576048Invitaecriteria provided, single submitter
Likely pathogenic
(Mar 11, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in FARS2 and non-fatal mitochondrial dysfunction in two siblings.

Vernon HJ, McClellan R, Batista DA, Naidu S.

Am J Med Genet A. 2015 May;167A(5):1147-51. doi: 10.1002/ajmg.a.36993. Epub 2015 Apr 6.

PubMed [citation]
PMID:
25851414

FARS2 deficiency; new cases, review of clinical, biochemical, and molecular spectra, and variants interpretation based on structural, functional, and evolutionary significance.

Almannai M, Wang J, Dai H, El-Hattab AW, Faqeih EA, Saleh MA, Al Asmari A, Alwadei AH, Aljadhai YI, AlHashem A, Tabarki B, Lines MA, Grange DK, Benini R, Alsaman AS, Mahmoud A, Katsonis P, Lichtarge O, Wong LC.

Mol Genet Metab. 2018 Nov;125(3):281-291. doi: 10.1016/j.ymgme.2018.07.014. Epub 2018 Jul 29.

PubMed [citation]
PMID:
30177229
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001576048.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine with cysteine at codon 419 of the FARS2 protein (p.Arg419Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs775690041, ExAC 0.003%). This variant has been observed in individual(s) with clinical features of hereditary spastic paraplegia (PMID: 25851414, 30177229). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 214336). 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: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 14, 2021

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