rs1553169975

Variant names:

• chr1-53213385-GAGCACACTGA-T
• rs1553169975
• NM_000098.3:c.1767_1777delGAGCACACTGAinsT

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000098.3(CPT2):​c.1767_1777delGAGCACACTGAinsT​(p.Ser590AlafsTer5) variant causes a frameshift, synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. T589T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPT2 NM_000098.3 frameshift, synonymous
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.91
• Publications: 0 publications found

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: Myriad Women’s Health, ClinGen
• carnitine palmitoyl transferase II deficiency, neonatal form

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• carnitine palmitoyl transferase II deficiency, myopathic form

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• carnitine palmitoyl transferase II deficiency, severe infantile form

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• encephalopathy, acute, infection-induced, susceptibility to, 4

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000236723 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 21 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-53213385-GAGCACACTGA-T is Pathogenic according to our data. Variant chr1-53213385-GAGCACACTGA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 529858.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000098.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT2	NM_000098.3	MANE Select	c.1767_1777delGAGCACACTGAinsT	p.Ser590AlafsTer5	frameshift synonymous	Exon 5 of 5	NP_000089.1	P23786
	CPT2	NM_001330589.2		c.1698_1708delGAGCACACTGAinsT	p.Ser567AlafsTer5	frameshift synonymous	Exon 5 of 5	NP_001317518.1	A0A1B0GTB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT2	ENST00000371486.4	TSL:1 MANE Select	c.1767_1777delGAGCACACTGAinsT	p.Ser590AlafsTer5	frameshift synonymous	Exon 5 of 5	ENSP00000360541.3	P23786
	CPT2	ENST00000873097.1		c.1833_1843delGAGCACACTGAinsT	p.Ser612AlafsTer5	frameshift synonymous	Exon 6 of 6	ENSP00000543156.1
	CPT2	ENST00000637252.1	TSL:5	c.1803_1813delGAGCACACTGAinsT	p.Ser602AlafsTer5	frameshift synonymous	Exon 6 of 6	ENSP00000490492.1	A0A1B0GVF3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Carnitine palmitoyltransferase II deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1553169975; hg19: chr1-53679057;