rs112070421
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_024537.4(CARS2):c.302G>T(p.Arg101Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,405,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R101Q) has been classified as Likely benign.
Frequency
Consequence
NM_024537.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARS2 | NM_024537.4 | c.302G>T | p.Arg101Leu | missense_variant | 3/15 | ENST00000257347.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARS2 | ENST00000257347.9 | c.302G>T | p.Arg101Leu | missense_variant | 3/15 | 1 | NM_024537.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000142 AC: 2AN: 1405844Hom.: 0 Cov.: 24 AF XY: 0.00000285 AC XY: 2AN XY: 702620
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 27 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | ClinVar contains an entry for this variant (Variation ID: 1505190). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 101 of the CARS2 protein (p.Arg101Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CARS2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at