NM_015836.4:c.*302A>G

Variant names:

• chr1-119032609-T-C
• rs1057990
• NM_015836.4:c.*302A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015836.4(WARS2):​c.*302A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 370,524 control chromosomes in the GnomAD database, including 14,563 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (7256 hom., cov: 33)
  • Exomes 𝑓: 0.25 (7307 hom.)
• Consequence: WARS2 NM_015836.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015836.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WARS2	NM_015836.4	MANE Select	c.*302A>G		3_prime_UTR	Exon 6 of 6	NP_056651.1	Q9UGM6-1
	WARS2	NM_001378226.1		c.*302A>G		3_prime_UTR	Exon 7 of 7	NP_001365155.1
	WARS2	NM_001378227.1		c.*302A>G		3_prime_UTR	Exon 8 of 8	NP_001365156.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WARS2	ENST00000235521.5	TSL:1 MANE Select	c.*302A>G		3_prime_UTR	Exon 6 of 6	ENSP00000235521.4	Q9UGM6-1
	WARS2	ENST00000369426.9	TSL:1	c.*751A>G		3_prime_UTR	Exon 6 of 6	ENSP00000358434.5	Q9UGM6-2
	WARS2	ENST00000928547.1		c.*302A>G		3_prime_UTR	Exon 7 of 7	ENSP00000598606.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44805 AN: 151936 Hom.: 7248 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.247 AC: 53913 AN: 218470 Hom.: 7307 Cov.: 0 AF XY: 0.246 AC XY: 27940 AN XY: 113698

African (AFR) AF: 0.420 AC: 2718 AN: 6472

American (AMR) AF: 0.153 AC: 1112 AN: 7258

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 1571 AN: 6880

East Asian (EAS) AF: 0.0901 AC: 1147 AN: 12726

South Asian (SAS) AF: 0.255 AC: 5673 AN: 22284

European-Finnish (FIN) AF: 0.253 AC: 3091 AN: 12216

Middle Eastern (MID) AF: 0.262 AC: 260 AN: 994

European-Non Finnish (NFE) AF: 0.256 AC: 35079 AN: 136804

Other (OTH) AF: 0.254 AC: 3262 AN: 12836

GnomAD4 genome AF: 0.295 AC: 44845 AN: 152054 Hom.: 7256 Cov.: 33 AF XY: 0.290 AC XY: 21526 AN XY: 74324

African (AFR) AF: 0.430 AC: 17830 AN: 41470

American (AMR) AF: 0.190 AC: 2910 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3470

East Asian (EAS) AF: 0.102 AC: 529 AN: 5174

South Asian (SAS) AF: 0.264 AC: 1272 AN: 4824

European-Finnish (FIN) AF: 0.260 AC: 2749 AN: 10568

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17763 AN: 67962

Other (OTH) AF: 0.264 AC: 556 AN: 2106

Alfa AF: 0.264 Hom.: 7216

Bravo AF: 0.292

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1057990; hg19: chr1-119575232;