Variant 3-108554433-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020890.3(CIP2A):c.2267A>G(p.Asn756Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,416,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.962

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04888153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CIP2A	NM_020890.3 linkuse as main transcript	c.2267A>G	p.Asn756Ser	missense_variant	18/21	ENST00000295746.13	NP_065941.2
CIP2A	XM_006713716.4 linkuse as main transcript	c.2264A>G	p.Asn755Ser	missense_variant	18/21		XP_006713779.1
CIP2A	XM_011513057.3 linkuse as main transcript	c.1325A>G	p.Asn442Ser	missense_variant	11/14		XP_011511359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIP2A	ENST00000295746.13 linkuse as main transcript	c.2267A>G	p.Asn756Ser	missense_variant	18/21	1	NM_020890.3	ENSP00000295746	P1	Q8TCG1-1
CIP2A	ENST00000491772.5 linkuse as main transcript	c.1790A>G	p.Asn597Ser	missense_variant	18/21	1		ENSP00000419487		Q8TCG1-2
CIP2A	ENST00000481530.5 linkuse as main transcript	c.*1837A>G		3_prime_UTR_variant, NMD_transcript_variant	18/21	1		ENSP00000417297

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000432

AC:

AN:

231730

Hom.:

AF XY:

0.00

AC XY:

AN XY:

124532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000972

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1416918

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

705794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2024

The c.2267A>G (p.N756S) alteration is located in exon 18 (coding exon 18) of the KIAA1524 gene. This alteration results from a A to G substitution at nucleotide position 2267, causing the asparagine (N) at amino acid position 756 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0046

T;.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.92

L;.;.

MutationTaster

Benign

0.62

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.30

N;N;.

REVEL

Benign

0.083

Sift

Benign

0.71

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.080

MutPred

0.094

Gain of glycosylation at T761 (P = 0.0375);.;.;

MVP

0.10

MPC

0.12

ClinPred

0.081

GERP RS

2.8

Varity_R

0.020

gMVP

0.046

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over