chr3-108554461-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020890.3(CIP2A):​c.2239G>C​(p.Asp747His) variant causes a missense change. The variant allele was found at a frequency of 0.00000295 in 1,354,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: CIP2A NM_020890.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.19
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24680096).

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.2239G>C	p.Asp747His	missense	Exon 18 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.2239G>C	p.Asp747His	missense	Exon 18 of 21	ENSP00000295746.7	Q8TCG1-1
	CIP2A	ENST00000491772.5	TSL:1	c.1762G>C	p.Asp588His	missense	Exon 18 of 21	ENSP00000419487.1	Q8TCG1-2
	CIP2A	ENST00000481530.5	TSL:1	n.*1809G>C		non_coding_transcript_exon	Exon 18 of 21	ENSP00000417297.1	F8WAX6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000481 AC: 1 AN: 207818 AF XY: 0.00000901

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000295 AC: 4 AN: 1354708 Hom.: 0 Cov.: 22 AF XY: 0.00000296 AC XY: 2 AN XY: 676464

African (AFR) AF: 0.00 AC: 0 AN: 31090

American (AMR) AF: 0.00 AC: 0 AN: 40096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25110

East Asian (EAS) AF: 0.00 AC: 0 AN: 38448

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5478

European-Non Finnish (NFE) AF: 0.00000292 AC: 3 AN: 1026628

Other (OTH) AF: 0.00 AC: 0 AN: 56598

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.9	M
PhyloP100		4.2
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.17
Sift	Benign	0.030	D
Sift4G	Uncertain	0.051	T
Polyphen		0.98	D
Vest4		0.29
MutPred		0.13		Gain of MoRF binding (P = 0.0443)
MVP		0.88
MPC		0.34
ClinPred		0.79	D
GERP RS		4.3
Varity_R		0.12
gMVP		0.23
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs767573515; hg19: chr3-108273308;