1-53211186-G-T

Variant names:

• chr1-53211186-G-T
• rs150953507
• NM_000098.3:c.1512G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_000098.3(CPT2):​c.1512G>T​(p.Pro504Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,608,258 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P504P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: CPT2 NM_000098.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -5.90
• Publications: 1 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 1-53211186-G-T is Benign according to our data. Variant chr1-53211186-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 509782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.9 with no splicing effect.

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.1512G>T	p.Pro504Pro	synonymous	Exon 4 of 5	NP_000089.1	P23786
	CPT2	NM_001330589.2		c.1512G>T	p.Pro504Pro	synonymous	Exon 4 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.1512G>T	p.Pro504Pro	synonymous	Exon 4 of 5	ENSP00000360541.3	P23786
	CPT2	ENST00000873097.1		c.1512G>T	p.Pro504Pro	synonymous	Exon 4 of 6	ENSP00000543156.1
	CPT2	ENST00000637252.1	TSL:5	c.1512G>T	p.Pro504Pro	synonymous	Exon 4 of 6	ENSP00000490492.1	A0A1B0GVF3

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 248 AN: 152148 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.00

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000365 AC: 90 AN: 246836 AF XY: 0.000217

Gnomad AFR exome AF: 0.00516

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000153 AC: 223 AN: 1455992 Hom.: 0 Cov.: 34 AF XY: 0.000122 AC XY: 88 AN XY: 723360

African (AFR) AF: 0.00537 AC: 179 AN: 33350

American (AMR) AF: 0.000225 AC: 10 AN: 44492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25792

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000902 AC: 10 AN: 1108038

Other (OTH) AF: 0.000383 AC: 23 AN: 60112

GnomAD4 genome AF: 0.00164 AC: 249 AN: 152266 Hom.: 1 Cov.: 32 AF XY: 0.00175 AC XY: 130 AN XY: 74444

African (AFR) AF: 0.00580 AC: 241 AN: 41558

American (AMR) AF: 0.000327 AC: 5 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00143 AC: 3 AN: 2104

Alfa AF: 0.00120 Hom.: 1

Bravo AF: 0.00167

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Carnitine palmitoyl transferase II deficiency, myopathic form (1)
-	-	1	Carnitine palmitoyl transferase II deficiency, neonatal form (1)
-	-	1	Carnitine palmitoyl transferase II deficiency, severe infantile form (1)
-	-	1	Carnitine palmitoyltransferase II deficiency (1)
-	-	1	CPT2-related disorder (1)
-	-	1	Encephalopathy, acute, infection-induced, susceptibility to, 4 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.021
DANN	Benign	0.77
PhyloP100		-5.9
Mutation Taster		=98/2	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

dbSNP: rs150953507; hg19: chr1-53676858;