NM_000098.3(CPT2):c.130C>T (p.His44Tyr) AND Carnitine palmitoyltransferase II deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 13, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001298969.7

Allele description [Variation Report for NM_000098.3(CPT2):c.130C>T (p.His44Tyr)]

NM_000098.3(CPT2):c.130C>T (p.His44Tyr)

Genes:

LOC129930561:ATAC-STARR-seq lymphoblastoid silent region 902 [Gene]
CPT2:carnitine palmitoyltransferase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p32.3

Genomic location:

Preferred name:

NM_000098.3(CPT2):c.130C>T (p.His44Tyr)

HGVS:

NC_000001.11:g.53197073C>T
NG_008035.1:g.5645C>T
NM_000098.3:c.130C>TMANE SELECT
NM_001330589.2:c.130C>T
NP_000089.1:p.His44Tyr
NP_001317518.1:p.His44Tyr
NC_000001.10:g.53662745C>T
NM_000098.2:c.130C>T

Protein change:

H44Y

Links:

dbSNP: rs995114769

NCBI 1000 Genomes Browser:

rs995114769

Molecular consequence:

NM_000098.3:c.130C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330589.2:c.130C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001488041	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002090257	Natera, Inc.	no assertion criteria provided	Uncertain significance (Oct 28, 2019)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001488041

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 13, 2022)

germline

clinical testing

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

SCV002090257

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Oct 28, 2019)

germline

clinical testing

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001488041.3

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

Description

This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 44 of the CPT2 protein (p.His44Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CPT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 585724). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CPT2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Natera, Inc., SCV002090257.1

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

#	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: May 7, 2024

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