rs1799822

Positions:

chr1-53213557-A-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.1939A>G(p.Met647Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,613,856 control chromosomes in the GnomAD database, including 33,516 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2188 hom., cov: 33)

Exomes 𝑓: 0.20 ( 31328 hom. )

Consequence

CPT2
NM_000098.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: 7.43

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:

(HGNC:):

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=0.0017347932).

BP6

Variant 1-53213557-A-G is Benign according to our data. Variant chr1-53213557-A-G is described in ClinVar as [Benign]. Clinvar id is 92433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-53213557-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 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.1939A>G	p.Met647Val	missense_variant	5/5	ENST00000371486.4	NP_000089.1
CPT2	NM_001330589.2 linkuse as main transcript	c.1870A>G	p.Met624Val	missense_variant	5/5		NP_001317518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT2	ENST00000371486.4 linkuse as main transcript	c.1939A>G	p.Met647Val	missense_variant	5/5	1	NM_000098.3	ENSP00000360541	P1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23057

AN:

152170

Hom.:

2187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0513

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.0817

Gnomad SAS

AF:

0.0948

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.164

AC:

41251

AN:

250846

Hom.:

3976

AF XY:

0.169

AC XY:

22871

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.0460

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.0839

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.200

AC:

292279

AN:

1461568

Hom.:

31328

Cov.:

AF XY:

0.198

AC XY:

144011

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0440

Gnomad4 AMR exome

AF:

0.130

Gnomad4 ASJ exome

AF:

0.256

Gnomad4 EAS exome

AF:

0.0669

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.197

GnomAD4 genome

AF:

0.152

AC:

23074

AN:

152288

Hom.:

2188

Cov.:

AF XY:

0.145

AC XY:

10783

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0515

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.251

Gnomad4 EAS

AF:

0.0821

Gnomad4 SAS

AF:

0.0943

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.187

Alfa

AF:

0.207

Hom.:

7833

Bravo

AF:

0.153

TwinsUK

AF:

0.221

AC:

821

ALSPAC

AF:

0.217

AC:

837

ESP6500AA

AF:

0.0545

AC:

240

ESP6500EA

AF:

0.225

AC:

1937

ExAC

AF:

0.162

AC:

19628

Asia WGS

AF:

0.0710

AC:

250

AN:

3476

EpiCase

AF:

0.228

EpiControl

AF:

0.232

ClinVar

Significance: Benign

Submissions summary: Benign:11Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Carnitine palmitoyltransferase II deficiency

Benign:3Other:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided, no classification provided	literature only	GeneReviews	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 04, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 29, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Carnitine palmitoyl transferase II deficiency, severe infantile form

Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -

Carnitine palmitoyl transferase II deficiency, neonatal form

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

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

Benign

0.078

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

T;.;T;T;T

Eigen

Benign

0.075

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.66

T;T;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.89

L;.;.;.;.

MutationTaster

Benign

0.0022

PrimateAI

Benign

0.28

PROVEAN

Benign

1.1

N;.;.;.;.

REVEL

Benign

0.28

Sift

Uncertain

0.021

D;.;.;.;.

Sift4G

Uncertain

0.010

D;.;.;.;.

Polyphen

0.0020

B;.;.;.;.

Vest4

0.071

MPC

0.12

ClinPred

0.013

GERP RS

5.9

Varity_R

0.23

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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