chr1-53196971-T-TAGCAAG
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000098.3(CPT2):c.28_29insAGCAAG(p.Trp10delinsTer) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000363 in 1,378,224 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000036 ( 0 hom. )
Consequence
CPT2
NM_000098.3 stop_gained
NM_000098.3 stop_gained
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.24
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 does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 128 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-53196971-T-TAGCAAG is Pathogenic according to our data. Variant chr1-53196971-T-TAGCAAG is described in ClinVar as [Pathogenic]. Clinvar id is 1073763.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.28_29insAGCAAG | p.Trp10delinsTer | stop_gained | 1/5 | ENST00000371486.4 | |
CPT2 | NM_001330589.2 | c.28_29insAGCAAG | p.Trp10delinsTer | stop_gained | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT2 | ENST00000371486.4 | c.28_29insAGCAAG | p.Trp10delinsTer | stop_gained | 1/5 | 1 | NM_000098.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.00000796 AC: 1AN: 125598Hom.: 0 AF XY: 0.0000144 AC XY: 1AN XY: 69646
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GnomAD4 exome AF: 0.00000363 AC: 5AN: 1378224Hom.: 0 Cov.: 30 AF XY: 0.00000735 AC XY: 5AN XY: 680726
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GnomAD4 genome ? Cov.: 32
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Cov.:
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Encephalopathy, acute, infection-induced, susceptibility to, 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 25, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 17, 2021 | - - |
Carnitine palmitoyltransferase II deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change creates a premature translational stop signal (p.Trp10*) 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). This variant is present in population databases (no rsID available, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with clinical features of carnitine palmitoyltransferase II deficiency (PMID: 30293990). ClinVar contains an entry for this variant (Variation ID: 1073763). For these reasons, this variant has been classified as Pathogenic. - |
Carnitine palmitoyl transferase II deficiency, severe infantile form Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at