3-108579413-C-A

Position:

• chr3-108579413-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020890.3(CIP2A):​c.686G>T​(p.Arg229Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIP2A	NM_020890.3	c.686G>T	p.Arg229Leu	missense_variant	7/21	ENST00000295746.13
CIP2A	XM_006713716.4	c.683G>T	p.Arg228Leu	missense_variant	7/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIP2A	ENST00000295746.13	c.686G>T	p.Arg229Leu	missense_variant	7/21	1	NM_020890.3	P1
CIP2A	ENST00000491772.5	c.209G>T	p.Arg70Leu	missense_variant	7/21	1
CIP2A	ENST00000487834.5	n.955G>T		non_coding_transcript_exon_variant	7/14	1
CIP2A	ENST00000481530.5	c.*256G>T		3_prime_UTR_variant, NMD_transcript_variant	7/21	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455500 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724214

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	0.0069	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T;.;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	0.00071	P;P
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.2	D;D;.
REVEL	Benign	0.093
Sift	Uncertain	0.0070	D;D;.
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.30	B;.;.
Vest4		0.62
MutPred		0.47		Gain of helix (P = 0.0696);.;Gain of helix (P = 0.0696);
MVP		0.60
MPC		0.41
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.67
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;