Variant chr1-53196971-T-TAGCAAG details in Genebe, Genetics Data Aggregator

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

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:4

Conservation

PhyloP100: 1.24

Variant links:

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]

CPT2 links:

Genome browser will be placed here

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 133 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 linkuse as main transcript	c.28_29insAGCAAG	p.Trp10delinsTer	stop_gained	1/5	ENST00000371486.4
CPT2	NM_001330589.2 linkuse as main transcript	c.28_29insAGCAAG	p.Trp10delinsTer	stop_gained	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT2	ENST00000371486.4 linkuse as main transcript	c.28_29insAGCAAG	p.Trp10delinsTer	stop_gained	1/5	1	NM_000098.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

125598

Hom.:

AF XY:

0.0000144

AC XY:

AN XY:

69646

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000461

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000363

AC:

AN:

1378224

Hom.:

Cov.:

AF XY:

0.00000735

AC XY:

AN XY:

680726

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000637

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 03, 2024

- -

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over