dbSNP rs761034141: CYP2J2:p.Arg321Leu (chr1-59907827-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000775.4(CYP2J2):c.962G>T(p.Arg321Leu) 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 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R321Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CYP2J2
NM_000775.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.771

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.962G>T	p.Arg321Leu	missense	Exon 6 of 9	NP_000766.2
CYP2J2	NR_134981.2		n.989G>T		non_coding_transcript_exon	Exon 6 of 8
CYP2J2	NR_134982.2		n.989G>T		non_coding_transcript_exon	Exon 6 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP2J2	ENST00000371204.4	TSL:1 MANE Select	c.962G>T	p.Arg321Leu	missense	Exon 6 of 9	ENSP00000360247.3	P51589
CYP2J2	ENST00000905907.1		c.953G>T	p.Arg318Leu	missense	Exon 6 of 9	ENSP00000575966.1
CYP2J2	ENST00000905910.1		c.962G>T	p.Arg321Leu	missense	Exon 6 of 9	ENSP00000575969.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111970

Other (OTH)

AF:

0.0000166

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

Eigen

Benign

-0.0014

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.4

PhyloP100

0.77

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.36

Sift

Benign

0.22

Sift4G

Benign

0.15

Polyphen

0.040

Vest4

0.32

MutPred

0.75

Gain of glycosylation at S317 (P = 0.1019)

MVP

0.74

MPC

0.44

ClinPred

0.96

GERP RS

5.6

Varity_R

0.37

gMVP

0.70

Mutation Taster

=75/25

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

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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