Genetic Variant CYP2J2:p.Glu477Lys (chr1-59893731-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000775.4(CYP2J2):c.1429G>A(p.Glu477Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CYP2J2
NM_000775.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.696

Publications

0 publications found

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]

CYP2J2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12504837).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000775.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CYP2J2	NM_000775.4	MANE Select	c.1429G>A	p.Glu477Lys	missense	Exon 9 of 9	NP_000766.2
CYP2J2	NR_134981.2		n.1268G>A		non_coding_transcript_exon	Exon 8 of 8
CYP2J2	NR_134982.2		n.1607G>A		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP2J2	ENST00000371204.4	TSL:1 MANE Select	c.1429G>A	p.Glu477Lys	missense	Exon 9 of 9	ENSP00000360247.3	P51589
CYP2J2	ENST00000905907.1		c.1420G>A	p.Glu474Lys	missense	Exon 9 of 9	ENSP00000575966.1
CYP2J2	ENST00000905910.1		c.1342G>A	p.Glu448Lys	missense	Exon 9 of 9	ENSP00000575969.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000799

AC:

AN:

250346

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460950

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726704

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.000101

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

85864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111622

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

-0.053

Eigen_PC

Benign

0.021

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.77

M_CAP

Benign

0.0080

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.52

PhyloP100

0.70

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

REVEL

Benign

0.19

Sift

Benign

0.065

Sift4G

Benign

0.080

Polyphen

0.22

Vest4

0.11

MutPred

0.41

Gain of MoRF binding (P = 0.0029)

MVP

0.76

MPC

0.17

ClinPred

0.31

GERP RS

4.7

Varity_R

0.14

gMVP

0.69

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over