rs1404944614

Variant names:

• chr3-108551316-A-G
• NM_020890.3:c.2551T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-108551316-A-G
• chr3-108551316-A-T

Variant summary

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

The NM_020890.3(CIP2A):​c.2551T>C​(p.Ser851Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,544 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: 6.9e-7 (0 hom.)
• Consequence: CIP2A NM_020890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.33

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]

MYH15 (HGNC:31073): (myosin heavy chain 15) Predicted to enable several functions, including ATP binding activity; actin filament binding activity; and calmodulin binding activity. Predicted to be involved in extraocular skeletal muscle development. Located in cytosol and intracellular membrane-bounded organelle. [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.2551T>C	p.Ser851Pro	missense_variant	Exon 21 of 21	ENST00000295746.13	NP_065941.2
CIP2A	XM_006713716.4	c.2548T>C	p.Ser850Pro	missense_variant	Exon 21 of 21		XP_006713779.1
CIP2A	XM_011513057.3	c.1609T>C	p.Ser537Pro	missense_variant	Exon 14 of 14		XP_011511359.1
MYH15	XM_011512559.3	c.-2032T>C		upstream_gene_variant			XP_011510861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIP2A	ENST00000295746.13	c.2551T>C	p.Ser851Pro	missense_variant	Exon 21 of 21	1	NM_020890.3	ENSP00000295746.7
CIP2A	ENST00000491772.5	c.2074T>C	p.Ser692Pro	missense_variant	Exon 21 of 21	1		ENSP00000419487.1
CIP2A	ENST00000481530.5	n.*2121T>C		non_coding_transcript_exon_variant	Exon 21 of 21	1		ENSP00000417297.1
CIP2A	ENST00000481530.5	n.*2121T>C		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000417297.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451544 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721850

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: 9.04e-7

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	0.99
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.6	D;D;.
REVEL	Benign	0.24
Sift	Uncertain	0.0080	D;D;.
Sift4G	Uncertain	0.034	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.60
MutPred		0.15		Gain of glycosylation at S847 (P = 0.0048);.;.;
MVP		0.84
MPC		0.72
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.75

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: chr3-108270163;