rs1799822

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M647I) has been classified as Likely 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

Publications

52 publications found

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 Gene-Disease associations (from GenCC):

carnitine palmitoyltransferase II deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women’s Health
carnitine palmitoyl transferase II deficiency, myopathic form
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
carnitine palmitoyl transferase II deficiency, neonatal form
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia
carnitine palmitoyl transferase II deficiency, severe infantile form
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet
encephalopathy, acute, infection-induced, susceptibility to, 4
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CPT2 links:

ENSG00000236723 (HGNC:):

ENSG00000236723 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 92433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
CPT2	NM_000098.3 link	c.1939A>G	p.Met647Val	missense_variant	Exon 5 of 5	ENST00000371486.4	NP_000089.1	P23786A0A140VK13
CPT2	NM_001330589.2 link	c.1870A>G	p.Met624Val	missense_variant	Exon 5 of 5		NP_001317518.1	A0A1B0GTB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT2	ENST00000371486.4 link	c.1939A>G	p.Met647Val	missense_variant	Exon 5 of 5	1	NM_000098.3	ENSP00000360541.3		P23786

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

GnomAD2 exomes

AF:

0.164

AC:

41251

AN:

250846

AF XY:

0.169

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 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

African (AFR)

AF:

0.0440

AC:

1472

AN:

33476

American (AMR)

AF:

0.130

AC:

5820

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

6679

AN:

26136

East Asian (EAS)

AF:

0.0669

AC:

2656

AN:

39700

South Asian (SAS)

AF:

0.103

AC:

8879

AN:

86252

European-Finnish (FIN)

AF:

0.134

AC:

7143

AN:

53416

Middle Eastern (MID)

AF:

0.172

AC:

974

AN:

5668

European-Non Finnish (NFE)

AF:

0.222

AC:

246784

AN:

1111814

Other (OTH)

AF:

0.197

AC:

11872

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

12482

24964

37445

49927

62409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8268

16536

24804

33072

41340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.152

AC:

23074

AN:

152288

Hom.:

2188

Cov.:

AF XY:

0.145

AC XY:

10783

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0515

AC:

2139

AN:

41562

American (AMR)

AF:

0.163

AC:

2499

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

872

AN:

3470

East Asian (EAS)

AF:

0.0821

AC:

426

AN:

5188

South Asian (SAS)

AF:

0.0943

AC:

455

AN:

4826

European-Finnish (FIN)

AF:

0.122

AC:

1299

AN:

10618

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14741

AN:

68004

Other (OTH)

AF:

0.187

AC:

394

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1005

2010

3015

4020

5025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.198

Hom.:

10852

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

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Aug 04, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 29, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 19, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Carnitine palmitoyl transferase II deficiency, neonatal form

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Aug 01, 2017

Phosphorus, Inc.

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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;.;.;.;.

PhyloP100

7.4

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

Mutation Taster

=62/38

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over