NM_006567.5(FARS2):c.1255C>T (p.Arg419Cys) AND Spastic paraplegia 77, autosomal recessive

Clinical significance:Likely pathogenic (Last evaluated: Jun 13, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000578139.2

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:
Spastic paraplegia 77, autosomal recessive (SPG77)
Identifiers:
MONDO: MONDO:0014882; MedGen: C4310750; OMIM: 617046

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000679998OMIMno assertion criteria providedPathogenic
(Jan 30, 2018)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000845719Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicinecriteria provided, single submitter
Likely pathogenic
(Jun 13, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineyesnot 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From OMIM, SCV000679998.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 2 sibs with mitochondrial dysfunction and spastic paraplegia (SPG77; 617046), Vernon et al. (2015) identified compound heterozygous mutations in the FARS2 gene: a paternally inherited c.1255C-T transition in exon 7, resulting in an arg419-to-cys (R419C) substitution at a conserved location in the phenylalanyl-RNA synthetase C-terminal domain, and a maternally inherited 116-kb interstitial deletion (nucleotides 5,610,223-5,726,369), including all of exon 6 and parts of introns 5 and 6. The mutations, which were found by exome sequencing and SNP array, respectively, were confirmed by Sanger sequencing. The missense mutation was not found in 6,500 individuals in the NHBLI Exome Sequencing Project database. Functional studies of the variants were not performed.

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

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV000845719.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 14, 2021

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