NM_000098.3:c.21G>T

Variant names:

• chr1-53196964-G-T
• NM_000098.3:c.21G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000098.3(CPT2):​c.21G>T​(p.Leu7Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CPT2 NM_000098.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0740
• 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: ClinGen, Myriad Women’s Health
• carnitine palmitoyl transferase II deficiency, myopathic form

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
• carnitine palmitoyl transferase II deficiency, neonatal form

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

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-53196964-G-T is Benign according to our data. Variant chr1-53196964-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2739194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.074 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT2	NM_000098.3	c.21G>T	p.Leu7Leu	synonymous_variant	Exon 1 of 5	ENST00000371486.4	NP_000089.1
CPT2	NM_001330589.2	c.21G>T	p.Leu7Leu	synonymous_variant	Exon 1 of 5		NP_001317518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT2	ENST00000371486.4	c.21G>T	p.Leu7Leu	synonymous_variant	Exon 1 of 5	1	NM_000098.3	ENSP00000360541.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1382588 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 683460

African (AFR) AF: 0.00 AC: 0 AN: 29462

American (AMR) AF: 0.00 AC: 0 AN: 37182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24734

East Asian (EAS) AF: 0.00 AC: 0 AN: 34548

South Asian (SAS) AF: 0.00 AC: 0 AN: 78770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4402

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080422

Other (OTH) AF: 0.00 AC: 0 AN: 57452

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Carnitine palmitoyltransferase II deficiency Benign:1

Jul 08, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.074
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr1-53662636;