chr3-108559786-G-T

Variant names:

• chr3-108559786-G-T
• NM_020890.3:c.1984C>A

Variant summary

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

The NM_020890.3(CIP2A):​c.1984C>A​(p.Arg662Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,435,504 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CIP2A NM_020890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.90

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 rank	MANE	Protein	UniProt
CIP2A	NM_020890.3	c.1984C>A	p.Arg662Ser	missense_variant	Exon 16 of 21	ENST00000295746.13	NP_065941.2
CIP2A	XM_006713716.4	c.1981C>A	p.Arg661Ser	missense_variant	Exon 16 of 21		XP_006713779.1
CIP2A	XM_011513057.3	c.1042C>A	p.Arg348Ser	missense_variant	Exon 9 of 14		XP_011511359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIP2A	ENST00000295746.13	c.1984C>A	p.Arg662Ser	missense_variant	Exon 16 of 21	1	NM_020890.3	ENSP00000295746.7
CIP2A	ENST00000491772.5	c.1507C>A	p.Arg503Ser	missense_variant	Exon 16 of 21	1		ENSP00000419487.1
CIP2A	ENST00000481530.5	n.*1554C>A		non_coding_transcript_exon_variant	Exon 16 of 21	1		ENSP00000417297.1
CIP2A	ENST00000481530.5	n.*1554C>A		3_prime_UTR_variant	Exon 16 of 21	1		ENSP00000417297.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1435504 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 709796

Gnomad4 AFR exome AF: 0.0000303

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	0.64
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T;.;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.7	D;D;.
REVEL	Uncertain	0.29
Sift	Uncertain	0.0030	D;D;.
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.81
MutPred		0.46		Gain of glycosylation at T666 (P = 0.0154);.;.;
MVP		0.61
MPC		0.68
ClinPred		0.96	D
GERP RS		6.0
Varity_R		0.60
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-108278633;