3-108560779-C-T

Position:

• chr3-108560779-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020890.3(CIP2A):​c.1697G>A​(p.Arg566Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CIP2A NM_020890.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

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]

ACMG classification

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=0.052405834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIP2A	NM_020890.3	c.1697G>A	p.Arg566Lys	missense_variant	14/21	ENST00000295746.13
CIP2A	XM_006713716.4	c.1694G>A	p.Arg565Lys	missense_variant	14/21
CIP2A	XM_011513057.3	c.755G>A	p.Arg252Lys	missense_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIP2A	ENST00000295746.13	c.1697G>A	p.Arg566Lys	missense_variant	14/21	1	NM_020890.3	P1
CIP2A	ENST00000491772.5	c.1220G>A	p.Arg407Lys	missense_variant	14/21	1
CIP2A	ENST00000487834.5	n.1970G>A		non_coding_transcript_exon_variant	14/14	1
CIP2A	ENST00000481530.5	c.*1267G>A		3_prime_UTR_variant, NMD_transcript_variant	14/21	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2023

The c.1697G>A (p.R566K) 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 1697, causing the arginine (R) at amino acid position 566 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	0.070
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.25
DEOGEN2	Benign	0.0013	T;.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.18	N;.;.
MutationTaster	Benign	0.82	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.49	N;N;.
REVEL	Benign	0.033
Sift	Benign	0.71	T;T;.
Sift4G	Benign	0.98	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.088
MutPred		0.30		Gain of methylation at R566 (P = 0.0068);.;.;
MVP		0.32
MPC		0.15
ClinPred		0.25	T
GERP RS		3.4
Varity_R		0.045
gMVP		0.20

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

Other links and lift over

dbSNP: rs1385705124; hg19: chr3-108279626;