ENST00000413531.5:n.38G>A

Variant names:

• chr1-119140767-G-A
• rs12096448
• ENST00000413531.5:n.38G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000413531.5(WARS2-AS1):​n.38G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 884,934 control chromosomes in the GnomAD database, including 33,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6798 hom., cov: 33)
  • Exomes 𝑓: 0.26 (26361 hom.)
• Consequence: WARS2-AS1 ENST00000413531.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.74
• Publications: 11 publications found

Genes affected

WARS2-AS1 (HGNC:40612): (WARS2 antisense RNA 1)

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]

WARS2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-119140767-G-A is Benign according to our data. Variant chr1-119140767-G-A is described in ClinVar as Benign. ClinVar VariationId is 1178536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000413531.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WARS2-AS1	NR_125974.1		n.372G>A		non_coding_transcript_exon	Exon 1 of 4
	WARS2-AS1	NR_125975.1		n.372G>A		non_coding_transcript_exon	Exon 1 of 7
	WARS2-AS1	NR_125976.1		n.372G>A		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WARS2-AS1	ENST00000413531.5	TSL:1	n.38G>A		non_coding_transcript_exon	Exon 1 of 5
	WARS2-AS1	ENST00000425884.7	TSL:1	n.372G>A		non_coding_transcript_exon	Exon 1 of 4
	WARS2-AS1	ENST00000440150.5	TSL:1	n.343G>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43766 AN: 152040 Hom.: 6789 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.0506

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.259 AC: 190049 AN: 732776 Hom.: 26361 Cov.: 10 AF XY: 0.260 AC XY: 96195 AN XY: 370264

African (AFR) AF: 0.390 AC: 6647 AN: 17050

American (AMR) AF: 0.146 AC: 2671 AN: 18288

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 4100 AN: 15160

East Asian (EAS) AF: 0.0444 AC: 1358 AN: 30588

South Asian (SAS) AF: 0.282 AC: 13953 AN: 49410

European-Finnish (FIN) AF: 0.243 AC: 7704 AN: 31640

Middle Eastern (MID) AF: 0.272 AC: 799 AN: 2942

European-Non Finnish (NFE) AF: 0.270 AC: 143856 AN: 533054

Other (OTH) AF: 0.259 AC: 8961 AN: 34644

GnomAD4 genome AF: 0.288 AC: 43800 AN: 152158 Hom.: 6798 Cov.: 33 AF XY: 0.281 AC XY: 20907 AN XY: 74384

African (AFR) AF: 0.392 AC: 16289 AN: 41520

American (AMR) AF: 0.189 AC: 2897 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 909 AN: 3470

East Asian (EAS) AF: 0.0503 AC: 259 AN: 5150

South Asian (SAS) AF: 0.283 AC: 1369 AN: 4832

European-Finnish (FIN) AF: 0.241 AC: 2549 AN: 10582

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18524 AN: 67982

Other (OTH) AF: 0.262 AC: 555 AN: 2116

Alfa AF: 0.0984 Hom.: 142

Bravo AF: 0.284

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.027
DANN	Benign	0.80
PhyloP100		-3.7
PromoterAI		-0.040	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12096448; hg19: chr1-119683390; COSMIC: COSV52480728;