1-119033110-G-C

Variant names:

• chr1-119033110-G-C
• NM_015836.4:c.884C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015836.4(WARS2):​c.884C>G​(p.Ala295Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A295V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WARS2 NM_015836.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06358799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WARS2	NM_015836.4	c.884C>G	p.Ala295Gly	missense_variant	Exon 6 of 6	ENST00000235521.5	NP_056651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WARS2	ENST00000235521.5	c.884C>G	p.Ala295Gly	missense_variant	Exon 6 of 6	1	NM_015836.4	ENSP00000235521.4
WARS2	ENST00000369426	c.*250C>G		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000358434.5
WARS2	ENST00000495746.5	n.*187C>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461814 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.5
DANN	Benign	0.94
DEOGEN2	Benign	0.083	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.95	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.026
Sift	Benign	0.24	T
Sift4G	Benign	0.37	T
Polyphen		0.0060	B
Vest4		0.091
MutPred		0.54		Gain of glycosylation at S294 (P = 0.0651);
MVP		0.068
MPC		0.69
ClinPred		0.042	T
GERP RS		0.70
Varity_R		0.13
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-119575733;