Genetic Variant CIP2A:p.Ile829Thr (chr3-108552295-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020890.3(CIP2A):c.2486T>C(p.Ile829Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000645 in 1,567,024 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.87

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06984314).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020890.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIP2A	NM_020890.3	MANE Select	c.2486T>C	p.Ile829Thr	missense	Exon 20 of 21	NP_065941.2	Q8TCG1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIP2A	ENST00000295746.13	TSL:1 MANE Select	c.2486T>C	p.Ile829Thr	missense	Exon 20 of 21	ENSP00000295746.7	Q8TCG1-1
CIP2A	ENST00000491772.5	TSL:1	c.2009T>C	p.Ile670Thr	missense	Exon 20 of 21	ENSP00000419487.1	Q8TCG1-2
CIP2A	ENST00000481530.5	TSL:1	n.*2056T>C		non_coding_transcript_exon	Exon 20 of 21	ENSP00000417297.1	F8WAX6

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000876

AC:

AN:

228308

AF XY:

0.0000647

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000418

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000566

Gnomad OTH exome

AF:

0.000359

GnomAD4 exome

AF:

0.0000466

AC:

AN:

1414898

Hom.:

Cov.:

AF XY:

0.0000369

AC XY:

AN XY:

705064

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31088

American (AMR)

AF:

0.000746

AC:

AN:

38848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25266

East Asian (EAS)

AF:

0.00

AC:

AN:

38900

South Asian (SAS)

AF:

0.00

AC:

AN:

80846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.0000314

AC:

AN:

1082794

Other (OTH)

AF:

0.0000512

AC:

AN:

58640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

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

AF:

0.000230

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41430

American (AMR)

AF:

0.000590

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68012

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000378

ExAC

AF:

0.0000659

AC:

ClinVar

ClinVar submissions as Germline

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

0.079

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

M_CAP

Benign

0.067

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.9

PhyloP100

7.9

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.25

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0080

Polyphen

0.47

Vest4

0.70

MVP

0.81

MPC

0.45

ClinPred

0.25

GERP RS

3.9

Varity_R

0.16

gMVP

0.31

Mutation Taster

=84/16

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over