GeneBe

rs7610357

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_015340.4(LARS2):​c.1053T>A​(p.Leu351Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L351L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LARS2
NM_015340.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0250

Publications

26 publications found
Variant links:
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]
LARS2-AS1 (HGNC:40796): (LARS2 antisense RNA 1)

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 3-45485726-T-A is Benign according to our data. Variant chr3-45485726-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 517084.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.025 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LARS2NM_015340.4 linkc.1053T>A p.Leu351Leu synonymous_variant Exon 11 of 22 ENST00000645846.2 NP_056155.1 Q15031

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LARS2ENST00000645846.2 linkc.1053T>A p.Leu351Leu synonymous_variant Exon 11 of 22 NM_015340.4 ENSP00000495093.1 Q15031

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1458952
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
725988
African (AFR)
AF:
0.00
AC:
0
AN:
33402
American (AMR)
AF:
0.00
AC:
0
AN:
43956
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26096
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39524
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53380
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1110756
Other (OTH)
AF:
0.00
AC:
0
AN:
60244
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
May 11, 2017
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
CADD
Benign
9.0
DANN
Benign
0.79
PhyloP100
-0.025

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

Other links and lift over

dbSNP: rs7610357; hg19: chr3-45527218; API