rs2229291

Positions:

chr1-53210729-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000098.3(CPT2):c.1055T>G(p.Phe352Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00891 in 1,614,208 control chromosomes in the GnomAD database, including 960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F352L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.017 ( 122 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 838 hom. )

Consequence

CPT2
NM_000098.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15O:1

Conservation

PhyloP100: 1.15

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:

CPT2 (HGNC:):

CPT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005623013).

BP6

Variant 1-53210729-T-G is Benign according to our data. Variant chr1-53210729-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 92428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-53210729-T-G is described in Lovd as [Benign]. Variant chr1-53210729-T-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT2	NM_000098.3 linkuse as main transcript	c.1055T>G	p.Phe352Cys	missense_variant	4/5	ENST00000371486.4	NP_000089.1	P23786A0A140VK13
CPT2	NM_001330589.2 linkuse as main transcript	c.1055T>G	p.Phe352Cys	missense_variant	4/5		NP_001317518.1	A0A1B0GTB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT2	ENST00000371486.4 linkuse as main transcript	c.1055T>G	p.Phe352Cys	missense_variant	4/5	1	NM_000098.3	ENSP00000360541.3		P23786

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2518

AN:

152208

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0349

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.0234

AC:

5870

AN:

251244

Hom.:

437

AF XY:

0.0202

AC XY:

2747

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.0404

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.206

Gnomad SAS exome

AF:

0.00412

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000881

Gnomad OTH exome

AF:

0.0143

GnomAD4 exome

AF:

0.00812

AC:

11868

AN:

1461882

Hom.:

838

Cov.:

AF XY:

0.00777

AC XY:

5654

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0228

Gnomad4 AMR exome

AF:

0.0397

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.00511

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000359

Gnomad4 OTH exome

AF:

0.00984

GnomAD4 genome

AF:

0.0165

AC:

2521

AN:

152326

Hom.:

122

Cov.:

AF XY:

0.0177

AC XY:

1316

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.0348

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.0103

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00976

Hom.:

235

Bravo

AF:

0.0213

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0202

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0218

AC:

2647

Asia WGS

AF:

0.0560

AC:

193

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:15Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 06, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 07, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 25156649, 23969168, 21277129, 20934285, 15811315, 9600456, 18306170, 21697855, 20981092, 16996287, 27884173, 30470651, 31351739, 25361188) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Carnitine palmitoyltransferase II deficiency

Benign:3Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 01, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 29, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 04, 2024	- -

Carnitine palmitoyl transferase II deficiency, neonatal form

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Carnitine palmitoyl transferase II deficiency, myopathic form

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Encephalopathy, acute, infection-induced, susceptibility to, 4

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

CPT2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 18, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Carnitine palmitoyl transferase II deficiency, severe infantile form

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Carnitine palmitoyl transferase II deficiency, severe infantile form;C1833518:Carnitine palmitoyl transferase II deficiency, neonatal form

Benign:1

Benign, criteria provided, single submitter

clinical testing

Phosphorus, Inc.

Aug 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.74

D;.;.;T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

D;D;D;D;D

MetaRNN

Benign

0.0056

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Pathogenic

3.3

M;.;.;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-7.0

D;.;.;.;.

REVEL

Uncertain

0.64

Sift

Pathogenic

0.0

D;.;.;.;.

Sift4G

Pathogenic

0.0010

D;.;.;.;.

Polyphen

1.0

D;.;.;.;.

Vest4

0.22

MPC

0.66

ClinPred

0.079

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.86

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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