chr1-53196962-C-CT
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000098.3(CPT2):c.20dup(p.Arg8AlafsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000195 in 1,536,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L7L) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CPT2
NM_000098.3 frameshift
NM_000098.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.665
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 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 129 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-53196962-C-CT is Pathogenic according to our data. Variant chr1-53196962-C-CT is described in ClinVar as [Pathogenic]. Clinvar id is 2795157.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT2 | NM_000098.3 | c.20dup | p.Arg8AlafsTer51 | frameshift_variant | 1/5 | ENST00000371486.4 | |
CPT2 | NM_001330589.2 | c.20dup | p.Arg8AlafsTer51 | frameshift_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT2 | ENST00000371486.4 | c.20dup | p.Arg8AlafsTer51 | frameshift_variant | 1/5 | 1 | NM_000098.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000145 AC: 2AN: 1384066Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 684318
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Carnitine palmitoyltransferase II deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 26, 2023 | For these reasons, this variant has been classified as Pathogenic. 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.Arg8Alafs*51) 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). - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at