Variant 3-108553711-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020890.3(CIP2A):c.2344G>A(p.Glu782Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000675 in 1,480,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000060 ( 0 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3869803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CIP2A	NM_020890.3 linkuse as main transcript	c.2344G>A	p.Glu782Lys	missense_variant	19/21	ENST00000295746.13
CIP2A	XM_006713716.4 linkuse as main transcript	c.2341G>A	p.Glu781Lys	missense_variant	19/21
CIP2A	XM_011513057.3 linkuse as main transcript	c.1402G>A	p.Glu468Lys	missense_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIP2A	ENST00000295746.13 linkuse as main transcript	c.2344G>A	p.Glu782Lys	missense_variant	19/21	1	NM_020890.3	P1	Q8TCG1-1
CIP2A	ENST00000491772.5 linkuse as main transcript	c.1867G>A	p.Glu623Lys	missense_variant	19/21	1			Q8TCG1-2
CIP2A	ENST00000481530.5 linkuse as main transcript	c.*1914G>A		3_prime_UTR_variant, NMD_transcript_variant	19/21	1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150608

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000601

AC:

AN:

1330020

Hom.:

Cov.:

AF XY:

0.00000897

AC XY:

AN XY:

669104

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:

0.00000704

Gnomad4 OTH exome

AF:

0.0000179

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150728

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73602

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

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

Jul 26, 2022

The c.2344G>A (p.E782K) alteration is located in exon 19 (coding exon 19) of the KIAA1524 gene. This alteration results from a G to A substitution at nucleotide position 2344, causing the glutamic acid (E) at amino acid position 782 to be replaced by a lysine (K). 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

0.13

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

T;.;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.2

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.83

N;N;.

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D;.

Sift4G

Uncertain

0.051

T;D;T

Polyphen

1.0

D;.;.

Vest4

0.54

MutPred

0.30

Gain of ubiquitination at E782 (P = 0.0016);.;.;

MVP

0.67

MPC

0.48

ClinPred

1.0

GERP RS

5.0

Varity_R

0.73

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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