rs142070578
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_024537.4(CARS2):c.1128C>T(p.Asp376=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,612,396 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0029 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0030 ( 8 hom. )
Consequence
CARS2
NM_024537.4 synonymous
NM_024537.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.466
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 13-110647166-G-A is Benign according to our data. Variant chr13-110647166-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.466 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00293 (446/152332) while in subpopulation NFE AF= 0.00378 (257/68026). AF 95% confidence interval is 0.0034. There are 0 homozygotes in gnomad4. There are 216 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARS2 | NM_024537.4 | c.1128C>T | p.Asp376= | synonymous_variant | 11/15 | ENST00000257347.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARS2 | ENST00000257347.9 | c.1128C>T | p.Asp376= | synonymous_variant | 11/15 | 1 | NM_024537.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00293 AC: 446AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00232 AC: 575AN: 247740Hom.: 3 AF XY: 0.00226 AC XY: 303AN XY: 134346
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GnomAD4 exome AF: 0.00304 AC: 4444AN: 1460064Hom.: 8 Cov.: 30 AF XY: 0.00292 AC XY: 2120AN XY: 726260
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GnomAD4 genome ? AF: 0.00293 AC: 446AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.00290 AC XY: 216AN XY: 74496
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 08, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | CARS2: BP4, BP7, BS2 - |
Combined oxidative phosphorylation defect type 27 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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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