1-119032674-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015836.4(WARS2):c.*237G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 517,860 control chromosomes in the GnomAD database, including 1,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.066 (458 hom., cov: 33)
  • Exomes 𝑓: 0.054 (844 hom.)
• Consequence: WARS2 NM_015836.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-119032674-C-G is Benign according to our data. Variant chr1-119032674-C-G is described in ClinVar as [Benign]. Clinvar id is 1251531.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WARS2	NM_015836.4	c.*237G>C		3_prime_UTR_variant	6/6	ENST00000235521.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WARS2	ENST00000235521.5	c.*237G>C		3_prime_UTR_variant	6/6	1	NM_015836.4	P1
WARS2	ENST00000369426.9	c.*686G>C		3_prime_UTR_variant	6/6	1

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10102 AN: 152138 Hom.: 452 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0531

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.0609

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.0636

GnomAD4 exome AF: 0.0542 AC: 19810 AN: 365604 Hom.: 844 Cov.: 4 AF XY: 0.0539 AC XY: 10285 AN XY: 190870

Gnomad4 AFR exome AF: 0.0981

Gnomad4 AMR exome AF: 0.0396

Gnomad4 ASJ exome AF: 0.0356

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.0542

Gnomad4 FIN exome AF: 0.0337

Gnomad4 NFE exome AF: 0.0430

Gnomad4 OTH exome AF: 0.0563

GnomAD4 genome AF: 0.0665 AC: 10119 AN: 152256 Hom.: 458 Cov.: 33 AF XY: 0.0653 AC XY: 4858 AN XY: 74436

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0531

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.0607

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0446

Gnomad4 OTH AF: 0.0719

Alfa AF: 0.0213 Hom.: 13

Bravo AF: 0.0681

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.37
Dann	Benign	0.74

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: rs3790548; hg19: chr1-119575297;