Variant 3-108551157-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_020890.3(CIP2A):c.2710A>G(p.Ser904Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000782 in 1,278,784 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: not found (cov: 31)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.48

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.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity CIP2A_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2637235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIP2A	NM_020890.3 linkuse as main transcript	c.2710A>G	p.Ser904Gly	missense_variant	21/21	ENST00000295746.13	NP_065941.2	Q8TCG1-1
CIP2A	XM_006713716.4 linkuse as main transcript	c.2707A>G	p.Ser903Gly	missense_variant	21/21		XP_006713779.1
CIP2A	XM_011513057.3 linkuse as main transcript	c.1768A>G	p.Ser590Gly	missense_variant	14/14		XP_011511359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CIP2A	ENST00000295746.13 linkuse as main transcript	c.2710A>G	p.Ser904Gly	missense_variant	21/21	1	NM_020890.3	ENSP00000295746.7	Q8TCG1-1
CIP2A	ENST00000491772.5 linkuse as main transcript	c.2233A>G	p.Ser745Gly	missense_variant	21/21	1		ENSP00000419487.1	Q8TCG1-2
CIP2A	ENST00000481530.5 linkuse as main transcript	n.*2280A>G		non_coding_transcript_exon_variant	21/21	1		ENSP00000417297.1	F8WAX6
CIP2A	ENST00000481530.5 linkuse as main transcript	n.*2280A>G		3_prime_UTR_variant	21/21	1		ENSP00000417297.1	F8WAX6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.82e-7

AC:

AN:

1278784

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

634270

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000396

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Jul 12, 2022

The c.2710A>G (p.S904G) alteration is located in exon 21 (coding exon 21) of the KIAA1524 gene. This alteration results from a A to G substitution at nucleotide position 2710, causing the serine (S) at amino acid position 904 to be replaced by a glycine (G). 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

0.20

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0073

T;.;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.54

N;N;.

REVEL

Benign

0.11

Sift

Uncertain

0.0040

D;D;.

Sift4G

Uncertain

0.011

D;D;D

Polyphen

0.97

D;.;.

Vest4

0.32

MutPred

0.36

Loss of stability (P = 0.0499);.;.;

MVP

0.48

MPC

0.38

ClinPred

0.79

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.69

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over