rs771193928
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_024537.4(CARS2):c.1431C>T(p.Asp477=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,607,864 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 (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
CARS2
NM_024537.4 synonymous
NM_024537.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.579
Genes affected
CARS2 (HGNC:25695): (cysteinyl-tRNA synthetase 2, mitochondrial) This gene encodes a putative member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of cysteine to tRNA molecules. A splice-site mutation in this gene has been associated with a novel progressive myoclonic epilepsy disease with similar symptoms to MERRF syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 13-110642507-G-A is Benign according to our data. Variant chr13-110642507-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475618.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.579 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARS2 | NM_024537.4 | c.1431C>T | p.Asp477= | synonymous_variant | 14/15 | ENST00000257347.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARS2 | ENST00000257347.9 | c.1431C>T | p.Asp477= | synonymous_variant | 14/15 | 1 | NM_024537.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152252Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000127 AC: 3AN: 236296Hom.: 0 AF XY: 0.0000234 AC XY: 3AN XY: 128260
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1455612Hom.: 0 Cov.: 33 AF XY: 0.0000166 AC XY: 12AN XY: 723538
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74380
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Combined oxidative phosphorylation defect type 27 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 16, 2023 | - - |
Computational scores
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Name
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Benign
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Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at