3-108579413-C-G

Position:

• chr3-108579413-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020890.3(CIP2A):​c.686G>C​(p.Arg229Pro) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R229Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIP2A NM_020890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIP2A	NM_020890.3	c.686G>C	p.Arg229Pro	missense_variant	7/21	ENST00000295746.13
CIP2A	XM_006713716.4	c.683G>C	p.Arg228Pro	missense_variant	7/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIP2A	ENST00000295746.13	c.686G>C	p.Arg229Pro	missense_variant	7/21	1	NM_020890.3	P1
CIP2A	ENST00000491772.5	c.209G>C	p.Arg70Pro	missense_variant	7/21	1
CIP2A	ENST00000487834.5	n.955G>C		non_coding_transcript_exon_variant	7/14	1
CIP2A	ENST00000481530.5	c.*256G>C		3_prime_UTR_variant, NMD_transcript_variant	7/21	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T;.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	0.00067	P;P
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.1	D;D;.
REVEL	Benign	0.22
Sift	Uncertain	0.0050	D;D;.
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.92	P;.;.
Vest4		0.68
MutPred		0.43		Gain of loop (P = 0.0435);.;Gain of loop (P = 0.0435);
MVP		0.71
MPC		0.65
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.92
gMVP		0.65

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: rs2278911; hg19: chr3-108298260;