dbSNP rs200502101: CIP2A:p.Ile829Ser (chr3-108552295-A-C) – 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_020890.3(CIP2A):c.2486T>G(p.Ile829Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,414,900 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. I829T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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: 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_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>G	p.Ile829Ser	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>G	p.Ile829Ser	missense	Exon 20 of 21	ENSP00000295746.7	Q8TCG1-1
CIP2A	ENST00000491772.5	TSL:1	c.2009T>G	p.Ile670Ser	missense	Exon 20 of 21	ENSP00000419487.1	Q8TCG1-2
CIP2A	ENST00000481530.5	TSL:1	n.*2056T>G		non_coding_transcript_exon	Exon 20 of 21	ENSP00000417297.1	F8WAX6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1414900

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

705066

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31088

American (AMR)

AF:

0.00

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:

0.00000277

AC:

AN:

1082796

Other (OTH)

AF:

0.00

AC:

AN:

58640

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0136242), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.079

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.9

PhyloP100

7.9

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.29

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.64

Vest4

0.80

MutPred

0.10

Gain of glycosylation at T828 (P = 0.0155)

MVP

0.81

MPC

0.64

ClinPred

0.98

GERP RS

3.9

Varity_R

0.42

gMVP

0.61

Mutation Taster

=79/21

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over