Genetic Variant NM_020890.3:c.2551T>A (chr3-108551316-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_020890.3(CIP2A):c.2551T>A(p.Ser851Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,544 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: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33

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:

MYH15 (HGNC:31073): (myosin heavy chain 15) Predicted to enable several functions, including ATP binding activity; actin filament binding activity; and calmodulin binding activity. Predicted to be involved in extraocular skeletal muscle development. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

MYH15 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=0.33846125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIP2A	NM_020890.3 link	c.2551T>A	p.Ser851Thr	missense_variant	Exon 21 of 21	ENST00000295746.13	NP_065941.2	Q8TCG1-1
CIP2A	XM_006713716.4 link	c.2548T>A	p.Ser850Thr	missense_variant	Exon 21 of 21		XP_006713779.1
CIP2A	XM_011513057.3 link	c.1609T>A	p.Ser537Thr	missense_variant	Exon 14 of 14		XP_011511359.1
MYH15	XM_011512559.3 link	c.-2032T>A		upstream_gene_variant			XP_011510861.1	Q9Y2K3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CIP2A	ENST00000295746.13 link	c.2551T>A	p.Ser851Thr	missense_variant	Exon 21 of 21	1	NM_020890.3	ENSP00000295746.7	Q8TCG1-1
CIP2A	ENST00000491772.5 link	c.2074T>A	p.Ser692Thr	missense_variant	Exon 21 of 21	1		ENSP00000419487.1	Q8TCG1-2
CIP2A	ENST00000481530.5 link	n.*2121T>A		non_coding_transcript_exon_variant	Exon 21 of 21	1		ENSP00000417297.1	F8WAX6
CIP2A	ENST00000481530.5 link	n.*2121T>A		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000417297.1	F8WAX6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246030

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133140

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:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451544

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721850

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:

0.0000119

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

Jun 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2551T>A (p.S851T) alteration is located in exon 21 (coding exon 21) of the KIAA1524 gene. This alteration results from a T to A substitution at nucleotide position 2551, causing the serine (S) at amino acid position 851 to be replaced by a threonine (T). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;.;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.2

M;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.1

N;N;.

REVEL

Benign

0.17

Sift

Uncertain

0.0060

D;D;.

Sift4G

Uncertain

0.041

D;T;D

Polyphen

1.0

D;.;.

Vest4

0.40

MutPred

0.11

Gain of glycosylation at S847 (P = 0.0048);.;.;

MVP

0.81

MPC

0.60

ClinPred

0.91

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.29

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