NM_015836.4(WARS2):c.791A>G (p.Tyr264Cys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 28, 2023
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:: RCV003387807.1

Allele description [Variation Report for NM_015836.4(WARS2):c.791A>G (p.Tyr264Cys)]

NM_015836.4(WARS2):c.791A>G (p.Tyr264Cys)

Gene:

WARS2:tryptophanyl tRNA synthetase 2, mitochondrial [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p12

Genomic location:

Preferred name:

NM_015836.4(WARS2):c.791A>G (p.Tyr264Cys)

HGVS:

NC_000001.11:g.119033203T>C
NG_050658.1:g.112586A>G
NM_001378226.1:c.722A>G
NM_001378227.1:c.722A>G
NM_001378228.1:c.620A>G
NM_001378229.1:c.533A>G
NM_001378230.1:c.509A>G
NM_001378231.1:c.*126A>G
NM_015836.4:c.791A>GMANE SELECT
NM_201263.2:c.*157A>G
NP_001365155.1:p.Tyr241Cys
NP_001365156.1:p.Tyr241Cys
NP_001365157.1:p.Tyr207Cys
NP_001365158.1:p.Tyr178Cys
NP_001365159.1:p.Tyr170Cys
NP_056651.1:p.Tyr264Cys
NC_000001.10:g.119575826T>C
NM_015836.3:c.791A>G

Protein change:

Y170C

Links:

dbSNP: rs139194636

NCBI 1000 Genomes Browser:

rs139194636

Molecular consequence:

NM_001378231.1:c.*126A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_201263.2:c.*157A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001378226.1:c.722A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378227.1:c.722A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378228.1:c.620A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378229.1:c.533A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378230.1:c.509A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_015836.4:c.791A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004100251	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Sep 28, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004100251

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Sep 28, 2023)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genomic diagnosis for children with intellectual disability and/or developmental delay.

Bowling KM, Thompson ML, Amaral MD, Finnila CR, Hiatt SM, Engel KL, Cochran JN, Brothers KB, East KM, Gray DE, Kelley WV, Lamb NE, Lose EJ, Rich CA, Simmons S, Whittle JS, Weaver BT, Nesmith AS, Myers RM, Barsh GS, Bebin EM, Cooper GM.

Genome Med. 2017 May 30;9(1):43. doi: 10.1186/s13073-017-0433-1.

PubMed [citation]

PMID:: 28554332
PMCID:: PMC5448144

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004100251.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: WARS2 c.791A>G (p.Tyr264Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 250944 control chromosomes (gnomAD). c.791A>G has been reported in the literature in an individual affected with WARS2-Related Disorders who was reported as compound heterozygous with a likely pathogenic variant (Bowling_2017). These data suggest the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 28554332). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as uncertain significance (n=3) or likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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