dbSNP rs371620733: CIP2A:p.Arg863Leu (chr3-108551279-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020890.3(CIP2A):c.2588G>T(p.Arg863Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,012 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 31)

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.19

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:

MYH15 (HGNC:31073): (myosin heavy chain 15) Predicted to enable several functions, including ATP binding activity; actin filament binding activity; and calmodulin binding activity. Predicted to be involved in extraocular skeletal muscle development. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

MYH15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15014529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIP2A	NM_020890.3 link	c.2588G>T	p.Arg863Leu	missense_variant	Exon 21 of 21	ENST00000295746.13	NP_065941.2	Q8TCG1-1
CIP2A	XM_006713716.4 link	c.2585G>T	p.Arg862Leu	missense_variant	Exon 21 of 21		XP_006713779.1
CIP2A	XM_011513057.3 link	c.1646G>T	p.Arg549Leu	missense_variant	Exon 14 of 14		XP_011511359.1
MYH15	XM_011512559.3 link	c.-1995G>T		upstream_gene_variant			XP_011510861.1	Q9Y2K3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CIP2A	ENST00000295746.13 link	c.2588G>T	p.Arg863Leu	missense_variant	Exon 21 of 21	1	NM_020890.3	ENSP00000295746.7	Q8TCG1-1
CIP2A	ENST00000491772.5 link	c.2111G>T	p.Arg704Leu	missense_variant	Exon 21 of 21	1		ENSP00000419487.1	Q8TCG1-2
CIP2A	ENST00000481530.5 link	n.*2158G>T		non_coding_transcript_exon_variant	Exon 21 of 21	1		ENSP00000417297.1	F8WAX6
CIP2A	ENST00000481530.5 link	n.*2158G>T		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000417297.1	F8WAX6

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152012

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:

0.000193

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.;T

Eigen

Benign

0.047

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.5

N;N;.

REVEL

Benign

0.10

Sift

Benign

0.37

T;T;.

Sift4G

Benign

0.28

T;T;T

Polyphen

0.030

B;.;.

Vest4

0.39

MutPred

0.14

Loss of methylation at R863 (P = 0.0428);.;.;

MVP

0.33

MPC

0.21

ClinPred

0.94

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over