Variant chr3-108559786-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020890.3(CIP2A):c.1984C>T(p.Arg662Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000241 in 1,587,616 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.90

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIP2A	NM_020890.3 linkuse as main transcript	c.1984C>T	p.Arg662Cys	missense_variant	16/21	ENST00000295746.13	NP_065941.2	Q8TCG1-1
CIP2A	XM_006713716.4 linkuse as main transcript	c.1981C>T	p.Arg661Cys	missense_variant	16/21		XP_006713779.1
CIP2A	XM_011513057.3 linkuse as main transcript	c.1042C>T	p.Arg348Cys	missense_variant	9/14		XP_011511359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CIP2A	ENST00000295746.13 linkuse as main transcript	c.1984C>T	p.Arg662Cys	missense_variant	16/21	1	NM_020890.3	ENSP00000295746.7	Q8TCG1-1
CIP2A	ENST00000491772.5 linkuse as main transcript	c.1507C>T	p.Arg503Cys	missense_variant	16/21	1		ENSP00000419487.1	Q8TCG1-2
CIP2A	ENST00000481530.5 linkuse as main transcript	n.*1554C>T		non_coding_transcript_exon_variant	16/21	1		ENSP00000417297.1	F8WAX6
CIP2A	ENST00000481530.5 linkuse as main transcript	n.*1554C>T		3_prime_UTR_variant	16/21	1		ENSP00000417297.1	F8WAX6

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152116

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:

0.000192

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000125

AC:

AN:

248228

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

134098

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000187

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000253

AC:

363

AN:

1435500

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

190

AN XY:

709794

show subpopulations

Gnomad4 AFR exome

AF:

0.0000908

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.000240

Gnomad4 FIN exome

AF:

0.000416

Gnomad4 NFE exome

AF:

0.000280

Gnomad4 OTH exome

AF:

0.000169

GnomAD4 genome

AF:

0.000131

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000182

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

AC:

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

Sep 29, 2023

The c.1984C>T (p.R662C) alteration is located in exon 16 (coding exon 16) of the KIAA1524 gene. This alteration results from a C to T substitution at nucleotide position 1984, causing the arginine (R) at amino acid position 662 to be replaced by a cysteine (C). 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

0.19

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

T;.;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.45

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.6

D;D;.

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.72

MVP

0.55

MPC

0.76

ClinPred

0.45

GERP RS

6.0

Varity_R

0.56

gMVP

0.55

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

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