rs34459812
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_015340.4(LARS2):āc.2124T>Cā(p.Ser708=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,614,064 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.011 ( 28 hom., cov: 32)
Exomes š: 0.0012 ( 34 hom. )
Consequence
LARS2
NM_015340.4 synonymous
NM_015340.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.62
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 3-45517982-T-C is Benign according to our data. Variant chr3-45517982-T-C is described in ClinVar as [Benign]. Clinvar id is 226699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.62 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1671/152308) while in subpopulation AFR AF= 0.0379 (1576/41572). AF 95% confidence interval is 0.0364. There are 28 homozygotes in gnomad4. There are 782 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 28 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LARS2 | NM_015340.4 | c.2124T>C | p.Ser708= | synonymous_variant | 18/22 | ENST00000645846.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LARS2 | ENST00000645846.2 | c.2124T>C | p.Ser708= | synonymous_variant | 18/22 | NM_015340.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0109 AC: 1662AN: 152190Hom.: 27 Cov.: 32
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GnomAD3 exomes AF: 0.00292 AC: 733AN: 251380Hom.: 11 AF XY: 0.00205 AC XY: 278AN XY: 135870
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GnomAD4 exome AF: 0.00121 AC: 1764AN: 1461756Hom.: 34 Cov.: 30 AF XY: 0.00109 AC XY: 793AN XY: 727192
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GnomAD4 genome ? AF: 0.0110 AC: 1671AN: 152308Hom.: 28 Cov.: 32 AF XY: 0.0105 AC XY: 782AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 15, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 25, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 06, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Ser708Ser in exon 18 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 4.1% (179/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs34459812). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 03, 2016 | 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. - |
LARS2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 22, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at