1-53210561-G-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PM5PP3_StrongPP5_Moderate
The NM_000098.3(CPT2):c.887G>C(p.Arg296Pro) variant causes a missense 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R296Q) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000098.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT2 | NM_000098.3 | c.887G>C | p.Arg296Pro | missense_variant | 4/5 | ENST00000371486.4 | |
CPT2 | NM_001330589.2 | c.887G>C | p.Arg296Pro | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT2 | ENST00000371486.4 | c.887G>C | p.Arg296Pro | missense_variant | 4/5 | 1 | NM_000098.3 | P1 | |
ENST00000629810.1 | n.286-152C>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Carnitine palmitoyltransferase II deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 05, 2018 | This sequence change replaces arginine with proline at codon 296 of the CPT2 protein (p.Arg296Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with CPT2 deficiency (Invitae database). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Other missense substitutions at this codon (p.Arg296Gln and p.Arg296Leu) have been reported in individuals affected with CPT2 deficiency (PMID: 14615409, 21913903). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at