NM_002047.4(GARS1):c.1660G>A (p.Asp554Asn) AND Distal hereditary motor neuronopathy type 5

Clinical significance:Uncertain significance (Last evaluated: Jun 16, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000009788.7

Allele description [Variation Report for NM_002047.4(GARS1):c.1660G>A (p.Asp554Asn)]

NM_002047.4(GARS1):c.1660G>A (p.Asp554Asn)

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.1660G>A (p.Asp554Asn)
HGVS:
  • NC_000007.14:g.30626280G>A
  • NG_007942.1:g.36716G>A
  • NM_001316772.1:c.1498G>A
  • NM_002047.4:c.1660G>AMANE SELECT
  • NP_001303701.1:p.Asp500Asn
  • NP_002038.2:p.Asp554Asn
  • LRG_243t1:c.1660G>A
  • LRG_243:g.36716G>A
  • NC_000007.13:g.30665896G>A
  • NM_002047.1:c.1498G>A
  • NM_002047.2:c.1660G>A
  • NM_002047.3:c.1660G>A
  • P41250:p.Asp554Asn
  • p.Asp500Asn
Protein change:
D500N; ASP500ASN
Links:
UniProtKB: P41250#VAR_073193; OMIM: 600287.0005; dbSNP: rs137852647
NCBI 1000 Genomes Browser:
rs137852647
Molecular consequence:
  • NM_001316772.1:c.1498G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002047.4:c.1660G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Distal hereditary motor neuronopathy type 5 (HMN5)
Synonyms:
NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE V; NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE VA; NEUROPATHY, DISTAL HEREDITARY MOTOR, TYPE VA; See all synonyms [MedGen]
Identifiers:
MedGen: C5399969; Orphanet: 139536; OMIM: 600794

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001322945Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Jun 16, 2017)
germlineclinical testing

Citation Link,

SCV001438348OMIMno assertion criteria providedPathogenic
(Nov 1, 2014)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Coexistence of CMT-2D and distal SMA-V phenotypes in an Italian family with a GARS gene mutation.

Del Bo R, Locatelli F, Corti S, Scarlato M, Ghezzi S, Prelle A, Fagiolari G, Moggio M, Carpo M, Bresolin N, Comi GP.

Neurology. 2006 Mar 14;66(5):752-4.

PubMed [citation]
PMID:
16534118

Impaired function is a common feature of neuropathy-associated glycyl-tRNA synthetase mutations.

Griffin LB, Sakaguchi R, McGuigan D, Gonzalez MA, Searby C, Z├╝chner S, Hou YM, Antonellis A.

Hum Mutat. 2014 Nov;35(11):1363-71. doi: 10.1002/humu.22681.

PubMed [citation]
PMID:
25168514
PMCID:
PMC4213347

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV001322945.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

From OMIM, SCV001438348.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a large Italian multigenerational family in which affected members had either Charcot-Marie-Tooth disease type 2D (CMT2D; 601472) or distal hereditary motor neuronopathy type VA (HMN5A; 600794), Del Bo et al. (2006) identified a heterozygous 2016G-A transition in exon 13 of the GARS gene, resulting in an asp500-to-asn (D500N) substitution. The mutation was not identified in 100 control Italian individuals. There was broad intrafamilial phenotype variability, with some members presenting symptoms in childhood and some in adulthood. Sensory involvement was variable. Functional studies of the variant were not performed.

Griffin et al. (2014) found that the D500N variant did not impair GARS function in 2 in vitro assays: the variant had normal enzyme activity and showed normal intracellular localization.

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

Last Updated: Jul 27, 2021

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