1-53210776-G-A

Position:

chr1-53210776-G-A

Variant summary

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

The NM_000098.3(CPT2):c.1102G>A(p.Val368Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 1,613,682 control chromosomes in the GnomAD database, including 222,450 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V368V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.46 ( 17298 hom., cov: 32)

Exomes 𝑓: 0.52 ( 205152 hom. )

Consequence

CPT2
NM_000098.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13O:1

Conservation

PhyloP100: -0.0480

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=1.4549217E-6).

BP6

Variant 1-53210776-G-A is Benign according to our data. Variant chr1-53210776-G-A is described in ClinVar as [Benign]. Clinvar id is 92429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-53210776-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 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.1102G>A	p.Val368Ile	missense_variant	4/5	ENST00000371486.4	NP_000089.1	P23786A0A140VK13
CPT2	NM_001330589.2 linkuse as main transcript	c.1102G>A	p.Val368Ile	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.1102G>A	p.Val368Ile	missense_variant	4/5	1	NM_000098.3	ENSP00000360541.3		P23786

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69707

AN:

151872

Hom.:

17289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.289

Gnomad AMI

AF:

0.685

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.499

Gnomad EAS

AF:

0.723

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.445

GnomAD3 exomes

AF:

0.488

AC:

122480

AN:

251146

Hom.:

31996

AF XY:

0.482

AC XY:

65378

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.282

Gnomad AMR exome

AF:

0.438

Gnomad ASJ exome

AF:

0.499

Gnomad EAS exome

AF:

0.728

Gnomad SAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.535

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.484

GnomAD4 exome

AF:

0.522

AC:

762983

AN:

1461692

Hom.:

205152

Cov.:

AF XY:

0.515

AC XY:

374539

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.432

Gnomad4 ASJ exome

AF:

0.498

Gnomad4 EAS exome

AF:

0.714

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.529

Gnomad4 NFE exome

AF:

0.548

Gnomad4 OTH exome

AF:

0.502

GnomAD4 genome

AF:

0.459

AC:

69747

AN:

151990

Hom.:

17298

Cov.:

AF XY:

0.454

AC XY:

33736

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.289

Gnomad4 AMR

AF:

0.449

Gnomad4 ASJ

AF:

0.499

Gnomad4 EAS

AF:

0.722

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.530

Gnomad4 NFE

AF:

0.542

Gnomad4 OTH

AF:

0.451

Alfa

AF:

0.522

Hom.:

53173

Bravo

AF:

0.452

TwinsUK

AF:

0.542

AC:

2009

ALSPAC

AF:

0.549

AC:

2116

ESP6500AA

AF:

0.290

AC:

1278

ESP6500EA

AF:

0.542

AC:

4658

ExAC

AF:

0.483

AC:

58689

Asia WGS

AF:

0.438

AC:

1523

AN:

3478

EpiCase

AF:

0.530

EpiControl

AF:

0.527

ClinVar

Significance: Benign

Submissions summary: Benign:13Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 04, 2015	- -

Carnitine palmitoyltransferase II deficiency

Benign:3Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
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	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
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 29, 2023	- -

Carnitine palmitoyl transferase II deficiency, neonatal form

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

CPT2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2019

This variant is classified as 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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.072

DANN

Benign

0.72

DEOGEN2

Benign

0.28

T;.;.;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.70

T;T;T;T;T

MetaRNN

Benign

0.0000015

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.74

N;.;.;.;.

PrimateAI

Benign

0.28

PROVEAN

Benign

0.11

N;.;.;.;.

REVEL

Benign

0.23

Sift

Benign

1.0

T;.;.;.;.

Sift4G

Benign

1.0

T;.;.;.;.

Polyphen

0.011

B;.;.;.;.

Vest4

0.028

MPC

0.095

ClinPred

0.0050

GERP RS

-0.26

Varity_R

0.010

gMVP

0.11

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