Variant 1-119140440-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378227.1(WARS2):c.-237C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 910,310 control chromosomes in the GnomAD database, including 34,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6635 hom., cov: 32)

Exomes 𝑓: 0.26 ( 27432 hom. )

Consequence

WARS2
NM_001378227.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.121

Variant links:

Genes affected

WARS2 (HGNC:12730): (tryptophanyl tRNA synthetase 2, mitochondrial) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Two forms of tryptophanyl-tRNA synthetase exist, a cytoplasmic form, named WARS, and a mitochondrial form, named WARS2. This gene encodes the mitochondrial tryptophanyl-tRNA synthetase. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

WARS2 links:

WARS2-AS1 (HGNC:):

WARS2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-119140440-G-A is Benign according to our data. Variant chr1-119140440-G-A is described in ClinVar as [Benign]. Clinvar id is 1227609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WARS2	NM_015836.4 linkuse as main transcript	c.90+115C>T		intron_variant		ENST00000235521.5	NP_056651.1	Q9UGM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WARS2	ENST00000235521.5 linkuse as main transcript	c.90+115C>T		intron_variant		1	NM_015836.4	ENSP00000235521.4		Q9UGM6-1
WARS2	ENST00000369426.9 linkuse as main transcript	c.90+115C>T		intron_variant		1		ENSP00000358434.5		Q9UGM6-2

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43303

AN:

152042

Hom.:

6628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.0470

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.261

AC:

197514

AN:

758150

Hom.:

27432

Cov.:

AF XY:

0.261

AC XY:

100537

AN XY:

385802

show subpopulations

Gnomad4 AFR exome

AF:

0.380

Gnomad4 AMR exome

AF:

0.137

Gnomad4 ASJ exome

AF:

0.270

Gnomad4 EAS exome

AF:

0.0439

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.241

Gnomad4 NFE exome

AF:

0.274

Gnomad4 OTH exome

AF:

0.259

GnomAD4 genome

AF:

0.285

AC:

43334

AN:

152160

Hom.:

6635

Cov.:

AF XY:

0.278

AC XY:

20697

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.257

Gnomad4 EAS

AF:

0.0467

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.241

Gnomad4 NFE

AF:

0.272

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.274

Hom.:

727

Bravo

AF:

0.281

Asia WGS

AF:

0.198

AC:

688

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.2

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over