3-108554461-C-A

Variant names:

• chr3-108554461-C-A
• rs767573515
• NM_020890.3:c.2239G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020890.3(CIP2A):​c.2239G>T​(p.Asp747Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000133 in 1,506,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: CIP2A NM_020890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.19

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 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=0.3026433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIP2A	NM_020890.3	c.2239G>T	p.Asp747Tyr	missense_variant	Exon 18 of 21	ENST00000295746.13	NP_065941.2
CIP2A	XM_006713716.4	c.2236G>T	p.Asp746Tyr	missense_variant	Exon 18 of 21		XP_006713779.1
CIP2A	XM_011513057.3	c.1297G>T	p.Asp433Tyr	missense_variant	Exon 11 of 14		XP_011511359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIP2A	ENST00000295746.13	c.2239G>T	p.Asp747Tyr	missense_variant	Exon 18 of 21	1	NM_020890.3	ENSP00000295746.7
CIP2A	ENST00000491772.5	c.1762G>T	p.Asp588Tyr	missense_variant	Exon 18 of 21	1		ENSP00000419487.1
CIP2A	ENST00000481530.5	n.*1809G>T		non_coding_transcript_exon_variant	Exon 18 of 21	1		ENSP00000417297.1
CIP2A	ENST00000481530.5	n.*1809G>T		3_prime_UTR_variant	Exon 18 of 21	1		ENSP00000417297.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1354708 Hom.: 0 Cov.: 22 AF XY: 0.00000148 AC XY: 1 AN XY: 676464

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000249

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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 AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74306

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.089	T;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.9	M;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.2	N;N;.
REVEL	Benign	0.19
Sift	Uncertain	0.016	D;D;.
Sift4G	Uncertain	0.022	D;D;D
Polyphen		0.98	D;.;.
Vest4		0.44
MutPred		0.14		Gain of MoRF binding (P = 0.043);.;.;
MVP		0.86
MPC		0.19
ClinPred		0.92	D
GERP RS		4.3
Varity_R		0.17
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs767573515; hg19: chr3-108273308;