1-119032609-T-C

Position:

• chr1-119032609-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WARS2	NM_015836.4	c.*302A>G		3_prime_UTR_variant	6/6	ENST00000235521.5	NP_056651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WARS2	ENST00000235521.5	c.*302A>G		3_prime_UTR_variant	6/6	1	NM_015836.4	ENSP00000235521	P1
WARS2	ENST00000369426.9	c.*751A>G		3_prime_UTR_variant	6/6	1		ENSP00000358434

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

Gnomad4 AFR exome AF: 0.420

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.0901

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.254

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

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.264

Alfa AF: 0.259 Hom.: 5248

Bravo AF: 0.292

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057990; hg19: chr1-119575232;