Variant 5-132747765-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001039780.4(CCNI2):c.270C>A(p.Asp90Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,470,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

CCNI2
NM_001039780.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.402

Variant links:

Genes affected

CCNI2 (HGNC:33869): (cyclin I family member 2) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in mitotic cell cycle phase transition and regulation of cyclin-dependent protein serine/threonine kinase activity. Predicted to be part of cyclin-dependent protein kinase holoenzyme complex. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CCNI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.063125044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNI2	NM_001039780.4 linkuse as main transcript	c.270C>A	p.Asp90Glu	missense_variant	1/6	ENST00000378731.6	NP_001034869.1	Q6ZMN8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNI2	ENST00000378731.6 linkuse as main transcript	c.270C>A	p.Asp90Glu	missense_variant	1/6	1	NM_001039780.4	ENSP00000368005.1		Q6ZMN8-1
CCNI2	ENST00000614847.1 linkuse as main transcript	c.270C>A	p.Asp90Glu	missense_variant	1/6	1		ENSP00000478257.1		Q6ZMN8-2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000987

AC:

AN:

1317714

Hom.:

Cov.:

AF XY:

0.0000108

AC XY:

AN XY:

648802

show subpopulations

Gnomad4 AFR exome

AF:

0.000262

Gnomad4 AMR exome

AF:

0.0000393

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000140

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.52e-7

Gnomad4 OTH exome

AF:

0.0000365

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.0000177

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.270C>A (p.D90E) alteration is located in exon 1 (coding exon 1) of the CCNI2 gene. This alteration results from a C to A substitution at nucleotide position 270, causing the aspartic acid (D) at amino acid position 90 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.1

DANN

Benign

0.91

DEOGEN2

Benign

0.0028

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.32

T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.46

N;.

REVEL

Benign

0.085

Sift

Benign

0.079

T;.

Sift4G

Benign

0.26

T;T

Polyphen

0.16

B;.

Vest4

0.068

MutPred

0.17

Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);

MVP

0.030

MPC

1.3

ClinPred

0.038

GERP RS

-1.9

Varity_R

0.061

gMVP

0.049

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over