Variant chr3-108560704-C-T 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.1772G>A(p.Gly591Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,458,732 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: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0730

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 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=0.029750317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CIP2A	NM_020890.3 linkuse as main transcript	c.1772G>A	p.Gly591Asp	missense_variant	14/21	ENST00000295746.13
CIP2A	XM_006713716.4 linkuse as main transcript	c.1769G>A	p.Gly590Asp	missense_variant	14/21
CIP2A	XM_011513057.3 linkuse as main transcript	c.830G>A	p.Gly277Asp	missense_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIP2A	ENST00000295746.13 linkuse as main transcript	c.1772G>A	p.Gly591Asp	missense_variant	14/21	1	NM_020890.3	P1	Q8TCG1-1
CIP2A	ENST00000491772.5 linkuse as main transcript	c.1295G>A	p.Gly432Asp	missense_variant	14/21	1			Q8TCG1-2
CIP2A	ENST00000481530.5 linkuse as main transcript	c.*1342G>A		3_prime_UTR_variant, NMD_transcript_variant	14/21	1
CIP2A	ENST00000487834.5 linkuse as main transcript			downstream_gene_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248798

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134336

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1458732

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725562

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 03, 2022

The c.1772G>A (p.G591D) alteration is located in exon 14 (coding exon 14) of the KIAA1524 gene. This alteration results from a G to A substitution at nucleotide position 1772, causing the glycine (G) at amino acid position 591 to be replaced by an aspartic acid (D). 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

0.070

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.7

DANN

Benign

0.46

DEOGEN2

Benign

0.00093

T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.030

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.87

N;N;.

REVEL

Benign

0.035

Sift

Benign

0.70

T;T;.

Sift4G

Benign

0.53

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.069

MutPred

0.23

Loss of catalytic residue at V592 (P = 0.1312);.;.;

MVP

0.23

MPC

0.19

ClinPred

0.0066

GERP RS

-1.2

Varity_R

0.022

gMVP

0.12

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