chr3-108554433-T-C

Position:

• chr3-108554433-T-C

Variant summary

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

The NM_020890.3(CIP2A):​c.2267A>G​(p.Asn756Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,416,918 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: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CIP2A NM_020890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962

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=0.04888153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIP2A	NM_020890.3	c.2267A>G	p.Asn756Ser	missense_variant	18/21	ENST00000295746.13
CIP2A	XM_006713716.4	c.2264A>G	p.Asn755Ser	missense_variant	18/21
CIP2A	XM_011513057.3	c.1325A>G	p.Asn442Ser	missense_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIP2A	ENST00000295746.13	c.2267A>G	p.Asn756Ser	missense_variant	18/21	1	NM_020890.3	P1
CIP2A	ENST00000491772.5	c.1790A>G	p.Asn597Ser	missense_variant	18/21	1
CIP2A	ENST00000481530.5	c.*1837A>G		3_prime_UTR_variant, NMD_transcript_variant	18/21	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000432 AC: 1 AN: 231730 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 124532

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000972

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1416918 Hom.: 0 Cov.: 24 AF XY: 0.00000283 AC XY: 2 AN XY: 705794

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000279

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.0046	T;.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.049	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.92	L;.;.
MutationTaster	Benign	0.62	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.30	N;N;.
REVEL	Benign	0.083
Sift	Benign	0.71	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.080
MutPred		0.094		Gain of glycosylation at T761 (P = 0.0375);.;.;
MVP		0.10
MPC		0.12
ClinPred		0.081	T
GERP RS		2.8
Varity_R		0.020
gMVP		0.046

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs894728622; hg19: chr3-108273280;