3-45485726-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015340.4(LARS2):c.1053T>C(p.Leu351Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 1,610,528 control chromosomes in the GnomAD database, including 695,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L351L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.80 ( 52820 hom., cov: 32)

Exomes 𝑓: 0.94 ( 642944 hom. )

Consequence

LARS2
NM_015340.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

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 links:

LARS2-AS1 (HGNC:40796): (LARS2 antisense RNA 1)

LARS2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 3-45485726-T-C is Benign according to our data. Variant chr3-45485726-T-C is described in ClinVar as Benign. ClinVar VariationId is 226691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.025 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARS2	NM_015340.4 link	c.1053T>C	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
LARS2	ENST00000645846.2 link	c.1053T>C	p.Leu351Leu	synonymous_variant	Exon 11 of 22		NM_015340.4	ENSP00000495093.1		Q15031

Frequencies

GnomAD3 genomes

AF:

0.800

AC:

121588

AN:

152062

Hom.:

52803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.422

Gnomad AMI

AF:

0.986

Gnomad AMR

AF:

0.905

Gnomad ASJ

AF:

0.889

Gnomad EAS

AF:

0.976

Gnomad SAS

AF:

0.921

Gnomad FIN

AF:

0.976

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.948

Gnomad OTH

AF:

0.826

GnomAD2 exomes

AF:

0.912

AC:

227498

AN:

249454

AF XY:

0.921

show subpopulations

Gnomad AFR exome

AF:

0.413

Gnomad AMR exome

AF:

0.946

Gnomad ASJ exome

AF:

0.885

Gnomad EAS exome

AF:

0.978

Gnomad FIN exome

AF:

0.973

Gnomad NFE exome

AF:

0.948

Gnomad OTH exome

AF:

0.919

GnomAD4 exome

AF:

0.935

AC:

1363611

AN:

1458348

Hom.:

642944

Cov.:

AF XY:

0.936

AC XY:

679546

AN XY:

725746

show subpopulations

African (AFR)

AF:

0.402

AC:

13418

AN:

33348

American (AMR)

AF:

0.940

AC:

41305

AN:

43938

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

23002

AN:

26076

East Asian (EAS)

AF:

0.977

AC:

38630

AN:

39520

South Asian (SAS)

AF:

0.929

AC:

79721

AN:

85790

European-Finnish (FIN)

AF:

0.971

AC:

51825

AN:

53380

Middle Eastern (MID)

AF:

0.885

AC:

5098

AN:

5758

European-Non Finnish (NFE)

AF:

0.951

AC:

1055935

AN:

1110322

Other (OTH)

AF:

0.908

AC:

54677

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

3320

6639

9959

13278

16598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21490

42980

64470

85960

107450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.799

AC:

121638

AN:

152180

Hom.:

52820

Cov.:

AF XY:

0.806

AC XY:

59943

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.422

AC:

17482

AN:

41462

American (AMR)

AF:

0.905

AC:

13826

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.889

AC:

3088

AN:

3472

East Asian (EAS)

AF:

0.976

AC:

5055

AN:

5180

South Asian (SAS)

AF:

0.921

AC:

4437

AN:

4820

European-Finnish (FIN)

AF:

0.976

AC:

10365

AN:

10622

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.948

AC:

64488

AN:

68030

Other (OTH)

AF:

0.827

AC:

1744

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

818

1636

2455

3273

4091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.873

Hom.:

32186

Bravo

AF:

0.775

Asia WGS

AF:

0.915

AC:

3182

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leu351Leu in exon 11 of LARS2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 44.0% (1937/4406) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs7610357). -

Dec 02, 2015

GeneDx

Significance: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. -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 16, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Perrault syndrome 4

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.5

(source)

DANN

Benign

0.77

PhyloP100

-0.025

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over