Genetic Variant CIP2A:p.Arg229Gln (chr3-108579413-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020890.3(CIP2A):c.686G>A(p.Arg229Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,605,506 control chromosomes in the GnomAD database, including 16,017 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1695 hom., cov: 32)

Exomes 𝑓: 0.12 ( 14322 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.58

Publications

34 publications found

Variant links:

Genes affected

CIP2A (HGNC:29302): (cellular inhibitor of PP2A) Enables protein homodimerization activity. Predicted to act upstream of or within positive regulation of neural precursor cell proliferation and spermatogenesis. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CIP2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012404919).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIP2A	NM_020890.3 link	c.686G>A	p.Arg229Gln	missense_variant	Exon 7 of 21	ENST00000295746.13	NP_065941.2	Q8TCG1-1
CIP2A	XM_006713716.4 link	c.683G>A	p.Arg228Gln	missense_variant	Exon 7 of 21		XP_006713779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIP2A	ENST00000295746.13 link	c.686G>A	p.Arg229Gln	missense_variant	Exon 7 of 21	1	NM_020890.3	ENSP00000295746.7		Q8TCG1-1

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19345

AN:

151808

Hom.:

1692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0999

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.128

GnomAD2 exomes

AF:

0.157

AC:

39020

AN:

248906

AF XY:

0.151

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.533

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.120

AC:

174261

AN:

1453580

Hom.:

14322

Cov.:

AF XY:

0.119

AC XY:

86272

AN XY:

723328

show subpopulations

African (AFR)

AF:

0.0940

AC:

3125

AN:

33246

American (AMR)

AF:

0.200

AC:

8904

AN:

44438

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3315

AN:

26024

East Asian (EAS)

AF:

0.526

AC:

20724

AN:

39436

South Asian (SAS)

AF:

0.116

AC:

9869

AN:

85262

European-Finnish (FIN)

AF:

0.140

AC:

7459

AN:

53374

Middle Eastern (MID)

AF:

0.113

AC:

652

AN:

5752

European-Non Finnish (NFE)

AF:

0.101

AC:

112144

AN:

1105948

Other (OTH)

AF:

0.134

AC:

8069

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

6386

12772

19157

25543

31929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4404

8808

13212

17616

22020

<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

AF:

0.127

AC:

19358

AN:

151926

Hom.:

1695

Cov.:

AF XY:

0.131

AC XY:

9745

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.0997

AC:

4131

AN:

41446

American (AMR)

AF:

0.157

AC:

2390

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

461

AN:

3468

East Asian (EAS)

AF:

0.525

AC:

2717

AN:

5178

South Asian (SAS)

AF:

0.123

AC:

590

AN:

4814

European-Finnish (FIN)

AF:

0.154

AC:

1619

AN:

10542

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

7004

AN:

67900

Other (OTH)

AF:

0.131

AC:

276

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

813

1627

2440

3254

4067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.119

Hom.:

5993

Bravo

AF:

0.130

TwinsUK

AF:

0.113

AC:

418

ALSPAC

AF:

0.102

AC:

392

ESP6500AA

AF:

0.0922

AC:

405

ESP6500EA

AF:

0.103

AC:

889

ExAC

AF:

0.152

AC:

18492

Asia WGS

AF:

0.289

AC:

1002

AN:

3472

EpiCase

AF:

0.103

EpiControl

AF:

0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0035

T;.;T

Eigen

Benign

0.099

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.88

D;D;D

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

L;.;.

PhyloP100

2.6

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.2

N;N;.

REVEL

Benign

0.066

Sift

Uncertain

0.016

D;D;.

Sift4G

Uncertain

0.037

D;D;D

Polyphen

0.14

B;.;.

Vest4

0.070

MPC

0.19

ClinPred

0.017

GERP RS

5.1

Varity_R

0.48

gMVP

0.12

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over