rs148035648

Variant names:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 3P and 10B. PM1PP3BP4_StrongBP6BS1BS2_Supporting

The NM_000098.3(CPT2):c.353A>G(p.Asp118Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000476 in 1,613,310 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D118D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 6 hom. )

Consequence

CPT2
NM_000098.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 8.95

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:

ENSG00000236723 (HGNC:):

ENSG00000236723 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_000098.3

PP3

Multiple lines of computational evidence support a deleterious effect 7: BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.015848875).

BP6

Variant 1-53210027-A-G is Benign according to our data. Variant chr1-53210027-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 203666.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=2, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000439 (641/1461524) while in subpopulation AMR AF= 0.0138 (618/44722). AF 95% confidence interval is 0.0129. There are 6 homozygotes in gnomad4_exome. There are 248 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 6 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT2	NM_000098.3 link	c.353A>G	p.Asp118Gly	missense_variant	Exon 4 of 5	ENST00000371486.4	NP_000089.1	P23786A0A140VK13
CPT2	NM_001330589.2 link	c.353A>G	p.Asp118Gly	missense_variant	Exon 4 of 5		NP_001317518.1	A0A1B0GTB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT2	ENST00000371486.4 link	c.353A>G	p.Asp118Gly	missense_variant	Exon 4 of 5	1	NM_000098.3	ENSP00000360541.3		P23786

Frequencies

GnomAD3 genomes

AF:

0.000837

AC:

127

AN:

151668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00728

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.00203

AC:

508

AN:

250816

Hom.:

AF XY:

0.00144

AC XY:

195

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.000316

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000439

AC:

641

AN:

1461524

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

248

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0138

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000837

AC:

127

AN:

151786

Hom.:

Cov.:

AF XY:

0.000850

AC XY:

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.00727

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.00150

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00165

AC:

200

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Apr 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 25, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Dec 10, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CPT2-related disorder

Benign:1

Jul 24, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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 palmitoyltransferase II deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

D;.;.;T;T

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D;D;D

MetaRNN

Benign

0.016

T;T;T;T;T

MetaSVM

Pathogenic

0.85

MutationAssessor

Pathogenic

3.9

H;.;.;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-6.2

D;.;.;.;.

REVEL

Pathogenic

0.94

Sift

Uncertain

0.0040

D;.;.;.;.

Sift4G

Uncertain

0.0050

D;.;.;.;.

Polyphen

0.98

D;.;.;.;.

Vest4

0.88

MVP

1.0

MPC

0.58

ClinPred

0.17

GERP RS

5.7

Varity_R

0.95

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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