dbSNP rs777271322: CIP2A:p.Thr828Ala (chr3-108552299-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020890.3(CIP2A):c.2482A>G(p.Thr828Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000701 in 1,569,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01880616).

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.2482A>G	p.Thr828Ala	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.2482A>G	p.Thr828Ala	missense	Exon 20 of 21	ENSP00000295746.7	Q8TCG1-1
CIP2A	ENST00000491772.5	TSL:1	c.2005A>G	p.Thr669Ala	missense	Exon 20 of 21	ENSP00000419487.1	Q8TCG1-2
CIP2A	ENST00000481530.5	TSL:1	n.*2052A>G		non_coding_transcript_exon	Exon 20 of 21	ENSP00000417297.1	F8WAX6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000573

AC:

AN:

226940

AF XY:

0.0000488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000789

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000635

AC:

AN:

1416856

Hom.:

Cov.:

AF XY:

0.00000850

AC XY:

AN XY:

705854

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31128

American (AMR)

AF:

0.00

AC:

AN:

38222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25200

East Asian (EAS)

AF:

0.000231

AC:

AN:

38964

South Asian (SAS)

AF:

0.00

AC:

AN:

80606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52820

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085622

Other (OTH)

AF:

0.00

AC:

AN:

58656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000385

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.0000264

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

0.068

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.9

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.010

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.79

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.61

M_CAP

Benign

0.010

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

1.5

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.98

REVEL

Benign

0.072

Sift

Benign

0.33

Sift4G

Benign

0.49

Polyphen

0.0010

Vest4

0.18

MutPred

0.11

Gain of glycosylation at T828 (P = 0.0155)

MVP

0.35

MPC

0.14

ClinPred

0.15

GERP RS

-3.5

Varity_R

0.024

gMVP

0.26

Mutation Taster

=80/20

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over