rs747618737
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2BP4_ModerateBP6_Very_StrongBP7BS1
The NM_015340.4(LARS2):āc.1104C>Gā(p.Gly368=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,608,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.0000089 ( 0 hom. )
Consequence
LARS2
NM_015340.4 synonymous
NM_015340.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.519
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 -13 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 3-45485777-C-G is Benign according to our data. Variant chr3-45485777-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 505003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.519 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000394 (6/152166) while in subpopulation EAS AF= 0.00115 (6/5200). AF 95% confidence interval is 0.000502. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LARS2 | NM_015340.4 | c.1104C>G | p.Gly368= | synonymous_variant | 11/22 | ENST00000645846.2 | |
LARS2-AS1 | NR_048543.1 | n.518-1746G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LARS2 | ENST00000645846.2 | c.1104C>G | p.Gly368= | synonymous_variant | 11/22 | NM_015340.4 | P1 | ||
LARS2-AS1 | ENST00000442534.2 | n.518-1746G>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000641 AC: 16AN: 249458Hom.: 0 AF XY: 0.0000519 AC XY: 7AN XY: 134946
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GnomAD4 exome AF: 0.00000893 AC: 13AN: 1455948Hom.: 0 Cov.: 29 AF XY: 0.00000966 AC XY: 7AN XY: 724726
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 02, 2016 | p.Gly368Gly in exon 11 of LARS2: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence. It has been identified in 0.1% (7/8651) of E ast Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs747618737). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 05, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at