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NM_002047.4(GARS1):c.1415A>G (p.His472Arg) AND not specified

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 13, 2019
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:
RCV004022757.1

Allele description [Variation Report for NM_002047.4(GARS1):c.1415A>G (p.His472Arg)]

NM_002047.4(GARS1):c.1415A>G (p.His472Arg)

Gene:
GARS1:glycyl-tRNA synthetase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p14.3
Genomic location:
Preferred name:
NM_002047.4(GARS1):c.1415A>G (p.His472Arg)
HGVS:
  • NC_000007.14:g.30621448A>G
  • NG_007942.1:g.31884A>G
  • NM_001316772.1:c.1253A>G
  • NM_002047.4:c.1415A>GMANE SELECT
  • NP_001303701.1:p.His418Arg
  • NP_002038.2:p.His472Arg
  • LRG_243t1:c.1415A>G
  • LRG_243:g.31884A>G
  • NC_000007.13:g.30661064A>G
  • NM_002047.1:c.1253A>G
  • NM_002047.2:c.1415A>G
  • NM_002047.3:c.1415A>G
  • p.His418Arg
Protein change:
H418R; HIS472ARG
Links:
OMIM: 600287.0013; dbSNP: rs1060502838
NCBI 1000 Genomes Browser:
rs1060502838
Molecular consequence:
  • NM_001316772.1:c.1253A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002047.4:c.1415A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002755192Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Nov 13, 2019) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Phenotypic spectrum of disorders associated with glycyl-tRNA synthetase mutations.

Sivakumar K, Kyriakides T, Puls I, Nicholson GA, Funalot B, Antonellis A, Sambuughin N, Christodoulou K, Beggs JL, Zamba-Papanicolaou E, Ionasescu V, Dalakas MC, Green ED, Fischbeck KH, Goldfarb LG.

Brain. 2005 Oct;128(Pt 10):2304-14. Epub 2005 Jul 13.

PubMed [citation]
PMID:
16014653

Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons.

Antonellis A, Lee-Lin SQ, Wasterlain A, Leo P, Quezado M, Goldfarb LG, Myung K, Burgess S, Fischbeck KH, Green ED.

J Neurosci. 2006 Oct 11;26(41):10397-406.

PubMed [citation]
PMID:
17035524
PMCID:
PMC6674701
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002755192.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The p.H472R variant (also known as c.1415A>G), located in coding exon 11 of the GARS gene, results from an A to G substitution at nucleotide position 1415. The histidine at codon 472 is replaced by arginine, an amino acid with highly similar properties. This variant (also referred to as p.H418R) has been reported in multiple patients with distal hereditary motor neuropathy (also called distal spinal muscular atrophy) and has been shown to segregate with disease (Sivakumar K et al. Brain, 2005 Oct;128:2304-14; Schabhüttl M et al. J. Neurol., 2014 May;261:970-82; Karakaya M et al. Hum. Mutat., 2018 09;39:1284-1298). Functional studies of this alteration demonstrate reduced aminoacylation activity, substantial reductions in yeast viability, and altered cellular localization in transfected mouse motor neuron cell lines (Griffin LB et al. Hum. Mutat., 2014 Nov;35:1363-71; Antonellis A et al. J. Neurosci., 2006 Oct;26:10397-406). In addition to the clinical data presented in the literature, this alteration is absent in population-based cohorts in the Genome Aggregation Database (gnomAD) and predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Oct 13, 2024