rs952621

chr3-45435202-G-A

Variant summary

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

The NM_015340.4(LARS2):c.517-11689G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,094 control chromosomes in the GnomAD database, including 2,088 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 0.16 (2088 hom., cov: 31)
• Consequence: LARS2 NM_015340.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.945

Genes affected

LARS2 (HGNC:17095): (leucyl-tRNA synthetase 2, mitochondrial) This gene encodes a class 1 aminoacyl-tRNA synthetase, mitochondrial leucyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. [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 = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LARS2	NM_015340.4	c.517-11689G>A		intron_variant		ENST00000645846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LARS2	ENST00000645846.2	c.517-11689G>A		intron_variant			NM_015340.4	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24890 AN: 151976 Hom.: 2085 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.164 AC: 24903 AN: 152094 Hom.: 2088 Cov.: 31 AF XY: 0.162 AC XY: 12009 AN XY: 74352

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.194

Alfa AF: 0.188 Hom.: 4777

Bravo AF: 0.167

Asia WGS AF: 0.143 AC: 497 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	1.7
Dann	Benign	0.57

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: rs952621; hg19: chr3-45476694;