Genetic Variant CYP2C18:p.Gln44Arg (chr10-94683950-A-G) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_000772.3(CYP2C18):c.131A>G(p.Gln44Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Q44L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CYP2C18
NM_000772.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.63

Publications

1 publications found

Variant links:

Genes affected

CYP2C18 (HGNC:2620): (cytochrome P450 family 2 subfamily C member 18) 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 but its specific substrate has not yet been determined. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. An additional gene, CYP2C17, was once thought to exist; however, CYP2C17 is now considered an artefact based on a chimera of CYP2C18 and CYP2C19. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CYP2C18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3 link	c.131A>G	p.Gln44Arg	missense_variant	Exon 1 of 9	ENST00000285979.11	NP_000763.1	P33260-1Q7Z348
CYP2C18	NM_001128925.2 link	c.131A>G	p.Gln44Arg	missense_variant	Exon 1 of 8		NP_001122397.1	P33260-2Q7Z348

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C18	ENST00000285979.11 link	c.131A>G	p.Gln44Arg	missense_variant	Exon 1 of 9	1	NM_000772.3	ENSP00000285979.6		P33260-1
CYP2C18	ENST00000339022.6 link	c.131A>G	p.Gln44Arg	missense_variant	Exon 1 of 8	1		ENSP00000341293.5		P33260-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725048

African (AFR)

AF:

0.00

AC:

AN:

33428

American (AMR)

AF:

0.00

AC:

AN:

44162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.00

AC:

AN:

85066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110270

Other (OTH)

AF:

0.00

AC:

AN:

60258

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.95

D;D

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.8

M;M

PhyloP100

4.6

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

0.38

B;.

Vest4

0.66

MutPred

0.82

Gain of MoRF binding (P = 0.0552);Gain of MoRF binding (P = 0.0552);

MVP

0.68

MPC

0.020

ClinPred

0.86

GERP RS

2.9

PromoterAI

0.042

Neutral

(source)

Varity_R

0.54

gMVP

0.47

Mutation Taster

=94/6

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over