3-108579413-C-G

Variant names:

• chr3-108579413-C-G
• rs2278911
• NM_020890.3:c.686G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIP2A NM_020890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58
• Publications: 34 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020890.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIP2A	NM_020890.3	MANE Select	c.686G>C	p.Arg229Pro	missense	Exon 7 of 21	NP_065941.2	Q8TCG1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIP2A	ENST00000295746.13	TSL:1 MANE Select	c.686G>C	p.Arg229Pro	missense	Exon 7 of 21	ENSP00000295746.7	Q8TCG1-1
	CIP2A	ENST00000491772.5	TSL:1	c.209G>C	p.Arg70Pro	missense	Exon 7 of 21	ENSP00000419487.1	Q8TCG1-2
	CIP2A	ENST00000481530.5	TSL:1	n.*256G>C		non_coding_transcript_exon	Exon 7 of 21	ENSP00000417297.1	F8WAX6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.6
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.22
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.013	D
Polyphen		0.92	P
Vest4		0.68
MutPred		0.43		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
Mutation Taster		=31/69	disease causing

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

Other links and lift over

dbSNP: rs2278911; hg19: chr3-108298260;