NM_012208.4(HARS2):c.448C>T (p.Arg150Cys) AND not specified

Clinical significance:Uncertain significance (Last evaluated: May 1, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000223531.2

Allele description [Variation Report for NM_012208.4(HARS2):c.448C>T (p.Arg150Cys)]

NM_012208.4(HARS2):c.448C>T (p.Arg150Cys)

Gene:
HARS2:histidyl-tRNA synthetase 2, mitochondrial [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q31.3
Genomic location:
Preferred name:
NM_012208.4(HARS2):c.448C>T (p.Arg150Cys)
Other names:
p.R150C:CGT>TGT
HGVS:
  • NC_000005.10:g.140695556C>T
  • NG_021415.1:g.9124C>T
  • NG_032158.1:g.831G>A
  • NM_001278731.2:c.373C>T
  • NM_001278732.2:c.94-182C>T
  • NM_001363535.2:c.466C>T
  • NM_001363536.2:c.238C>T
  • NM_012208.4:c.448C>TMANE SELECT
  • NP_001265660.1:p.Arg125Cys
  • NP_001350464.1:p.Arg156Cys
  • NP_001350465.1:p.Arg80Cys
  • NP_036340.1:p.Arg150Cys
  • LRG_1376t1:c.448C>T
  • LRG_1374:g.831G>A
  • LRG_1376:g.9124C>T
  • LRG_1376p1:p.Arg150Cys
  • NC_000005.9:g.140075141C>T
  • NM_012208.2:c.448C>T
  • NM_012208.3:c.448C>T
Protein change:
R125C
Links:
dbSNP: rs140540222
NCBI 1000 Genomes Browser:
rs140540222
Molecular consequence:
  • NM_001278732.2:c.94-182C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001278731.2:c.373C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363535.2:c.466C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363536.2:c.238C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012208.4:c.448C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000271834Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(May 1, 2016)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided21not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000271834.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg150Cys variant in HARS2 has been reported by our laboratory in one individual with hea ring loss who was compound heterozygous for a second variant of uncertain signif icance in the HARS2 gene (this family). This variant has been identified in 6/1 21406 total chromosomes across all populations by the Exome Aggregation Consorti um (ExAC, http://exac.broadinstitute.org; dbSNP rs140540222). Although this vari ant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools suggest that the p.A rg150Cys variant may impact the protein, though this information is not predicti ve enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Arg150Cys variant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided1not provided

Last Updated: Jan 8, 2022

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