chr1-53210194-G-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000098.3(CPT2):c.520G>T(p.Glu174Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
CPT2
NM_000098.3 stop_gained
NM_000098.3 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
CPT2 (HGNC:2330): (carnitine palmitoyltransferase 2) The protein encoded by this gene is a nuclear protein which is transported to the mitochondrial inner membrane. Together with carnitine palmitoyltransferase I, the encoded protein oxidizes long-chain fatty acids in the mitochondria. Defects in this gene are associated with mitochondrial long-chain fatty-acid (LCFA) oxidation disorders. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-53210194-G-T is Pathogenic according to our data. Variant chr1-53210194-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 550520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT2 | NM_000098.3 | c.520G>T | p.Glu174Ter | stop_gained | 4/5 | ENST00000371486.4 | |
CPT2 | NM_001330589.2 | c.520G>T | p.Glu174Ter | stop_gained | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT2 | ENST00000371486.4 | c.520G>T | p.Glu174Ter | stop_gained | 4/5 | 1 | NM_000098.3 | P1 | |
ENST00000629810.1 | n.424C>A | non_coding_transcript_exon_variant | 3/3 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Carnitine palmitoyl transferase II deficiency, severe infantile form Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jan 26, 2017 | - - |
Carnitine palmitoyltransferase II deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2021 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 550520). This variant has not been reported in the literature in individuals affected with CPT2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu174*) in the CPT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPT2 are known to be pathogenic (PMID: 16781677, 16996287). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at