rs766154927

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000775.4(CYP2J2):​c.1093G>C​(p.Val365Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V365I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

CYP2J2
NM_000775.4 missense

Scores

5
11
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.09
Variant links:
Genes affected
CYP2J2 (HGNC:2634): (cytochrome P450 family 2 subfamily J member 2) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is thought to be the predominant enzyme responsible for epoxidation of endogenous arachidonic acid in cardiac tissue. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYP2J2NM_000775.4 linkc.1093G>C p.Val365Leu missense_variant Exon 7 of 9 ENST00000371204.4 NP_000766.2 P51589

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYP2J2ENST00000371204.4 linkc.1093G>C p.Val365Leu missense_variant Exon 7 of 9 1 NM_000775.4 ENSP00000360247.3 P51589

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461538
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727056
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.022
T
MetaRNN
Pathogenic
0.87
D
MetaSVM
Uncertain
0.79
D
MutationAssessor
Pathogenic
3.7
H
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-2.6
D
REVEL
Pathogenic
0.71
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0060
D
Polyphen
0.98
D
Vest4
0.67
MutPred
0.73
Gain of glycosylation at P360 (P = 0.1627);
MVP
0.83
MPC
0.51
ClinPred
0.98
D
GERP RS
4.0
Varity_R
0.46
gMVP
0.67

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs766154927; hg19: chr1-60370641; API