rs141996297
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_024537.4(CARS2):c.1317+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00706 in 1,610,366 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0058 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0072 ( 63 hom. )
Consequence
CARS2
NM_024537.4 intron
NM_024537.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.365
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 13-110645957-G-A is Benign according to our data. Variant chr13-110645957-G-A is described in ClinVar as [Benign]. Clinvar id is 382608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00585 (891/152316) while in subpopulation SAS AF= 0.0108 (52/4832). AF 95% confidence interval is 0.00843. There are 6 homozygotes in gnomad4. There are 425 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CARS2 | NM_024537.4 | c.1317+10C>T | intron_variant | ENST00000257347.9 | NP_078813.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CARS2 | ENST00000257347.9 | c.1317+10C>T | intron_variant | 1 | NM_024537.4 | ENSP00000257347 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00587 AC: 893AN: 152198Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00747 AC: 1842AN: 246726Hom.: 9 AF XY: 0.00806 AC XY: 1076AN XY: 133460
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GnomAD4 exome AF: 0.00719 AC: 10479AN: 1458050Hom.: 63 Cov.: 30 AF XY: 0.00752 AC XY: 5453AN XY: 725350
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GnomAD4 genome AF: 0.00585 AC: 891AN: 152316Hom.: 6 Cov.: 32 AF XY: 0.00571 AC XY: 425AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 11, 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. - |
Combined oxidative phosphorylation defect type 27 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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