chr1-119084604-C-T

Position:

• chr1-119084604-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015836.4(WARS2):​c.91-7997G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,116 control chromosomes in the GnomAD database, including 4,171 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 0.23 (4171 hom., cov: 32)
• Consequence: WARS2 NM_015836.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WARS2	NM_015836.4	c.91-7997G>A		intron_variant		ENST00000235521.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WARS2	ENST00000235521.5	c.91-7997G>A		intron_variant		1	NM_015836.4	P1
WARS2	ENST00000369426.9	c.91-7997G>A		intron_variant		1
WARS2	ENST00000495746.5	n.101-7997G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34754 AN: 151998 Hom.: 4172 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.229 AC: 34766 AN: 152116 Hom.: 4171 Cov.: 32 AF XY: 0.225 AC XY: 16747 AN XY: 74350

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.0721

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.217

Alfa AF: 0.226 Hom.: 649

Bravo AF: 0.219

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.61

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: rs10802075; hg19: chr1-119627227;