NM_000098.3(CPT2):c.1569_1570del (p.His523fs) AND Carnitine palmitoyltransferase II deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Sep 26, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000781317.4

Allele description [Variation Report for NM_000098.3(CPT2):c.1569_1570del (p.His523fs)]

NM_000098.3(CPT2):c.1569_1570del (p.His523fs)

Gene:

CPT2:carnitine palmitoyltransferase 2 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

1p32.3

Genomic location:

Preferred name:

NM_000098.3(CPT2):c.1569_1570del (p.His523fs)

HGVS:

NC_000001.10:g.53676913_53676914del
NC_000001.11:g.53211241CA[1]
NG_008035.1:g.19813CA[1]
NM_000098.3:c.1569_1570delMANE SELECT
NM_001330589.2:c.1569_1570del
NP_000089.1:p.His523fs
NP_001317518.1:p.His523fs
NC_000001.10:g.53676913CA[1]
NC_000001.10:g.53676913_53676914del
NC_000001.10:g.53676915_53676916delCA
NM_000098.2:c.1569_1570delCA

Protein change:

H523fs

Links:

dbSNP: rs1572385947

NCBI 1000 Genomes Browser:

rs1572385947

Molecular consequence:

NM_000098.3:c.1569_1570del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330589.2:c.1569_1570del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Carnitine palmitoyltransferase II deficiency (CPT2)
Synonyms:: Carnitine palmitoyl transferase 2 deficiency; Carnitine palmitoyltransferase deficiency type 2
Identifiers:: MONDO: MONDO:0015515; MedGen: C0342790

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000919248	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jul 12, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002233597	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 26, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16781677, 16996287, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000919248

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jul 12, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV002233597

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 26, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Crystal structure of rat carnitine palmitoyltransferase II (CPT-II).

Hsiao YS, Jogl G, Esser V, Tong L.

Biochem Biophys Res Commun. 2006 Aug 4;346(3):974-80. Epub 2006 Jun 9.

PubMed [citation]

PMID:: 16781677
PMCID:: PMC2937350

Identification of 16 new disease-causing mutations in the CPT2 gene resulting in carnitine palmitoyltransferase II deficiency.

Isackson PJ, Bennett MJ, Vladutiu GD.

Mol Genet Metab. 2006 Dec;89(4):323-31. Epub 2006 Sep 22.

PubMed [citation]

PMID:: 16996287

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919248.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: CPT2 c.1569_1570delCA (p.His523GlnfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 102738 control chromosomes. c.1569_1570delCA has been reported in the literature in a healthy newborn with elevated levels of long chain acylcarnitines, with the pathogenic variant c.338C>T (p.Ser113Leu) in trans (Isackson 2006). Authors of this study concluded that this patient will be at risk for developing the adult onset form of CPT II deficiency. However these data do not allow unequivocal conclusions about variant significance. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV002233597.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 633182). This premature translational stop signal has been observed in individual(s) with elevated long chain acylcarnitine levels (PMID: 16996287). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.His523Glnfs*4) in the CPT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPT2 are known to be pathogenic (PMID: 16781677, 16996287).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 14, 2024

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