1-119084604-C-T

Variant names:

• chr1-119084604-C-T
• rs10802075
• NM_015836.4:c.91-7997G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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]

RBMX2P3 (HGNC:39925): (RBMX2 pseudogene 3)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WARS2	NM_015836.4	MANE Select	c.91-7997G>A		intron	N/A	NP_056651.1
	WARS2	NM_001378226.1		c.22-7997G>A		intron	N/A	NP_001365155.1
	WARS2	NM_001378227.1		c.22-7997G>A		intron	N/A	NP_001365156.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WARS2	ENST00000235521.5	TSL:1 MANE Select	c.91-7997G>A		intron	N/A	ENSP00000235521.4
	WARS2	ENST00000369426.9	TSL:1	c.91-7997G>A		intron	N/A	ENSP00000358434.5
	WARS2	ENST00000495746.5	TSL:2	n.101-7997G>A		intron	N/A

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

African (AFR) AF: 0.213 AC: 8826 AN: 41484

American (AMR) AF: 0.161 AC: 2463 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3468

East Asian (EAS) AF: 0.0721 AC: 374 AN: 5186

South Asian (SAS) AF: 0.241 AC: 1159 AN: 4806

European-Finnish (FIN) AF: 0.258 AC: 2734 AN: 10580

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17575 AN: 67978

Other (OTH) AF: 0.217 AC: 457 AN: 2108

Alfa AF: 0.226 Hom.: 675

Bravo AF: 0.219

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.61
PhyloP100		-0.44
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: rs10802075; hg19: chr1-119627227;