Variant 5-132747849-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039780.4(CCNI2):c.354C>A(p.Asp118Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,320,250 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: not found (cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

CCNI2
NM_001039780.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.95

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.073183596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNI2	NM_001039780.4 linkuse as main transcript	c.354C>A	p.Asp118Glu	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.354C>A	p.Asp118Glu	missense_variant	1/6	1	NM_001039780.4	ENSP00000368005.1		Q6ZMN8-1
CCNI2	ENST00000614847.1 linkuse as main transcript	c.354C>A	p.Asp118Glu	missense_variant	1/6	1		ENSP00000478257.1		Q6ZMN8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000182

AC:

AN:

1320250

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

650226

show subpopulations

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:

0.0000228

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 14, 2023

The c.354C>A (p.D118E) 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 354, causing the aspartic acid (D) at amino acid position 118 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

0.20

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.13

DANN

Benign

0.69

DEOGEN2

Benign

0.00069

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.81

L;L

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.030

N;.

REVEL

Benign

0.031

Sift

Benign

0.38

T;.

Sift4G

Benign

0.56

T;T

Polyphen

0.11

B;.

Vest4

0.067

MutPred

0.53

Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);

MVP

0.21

MPC

1.3

ClinPred

0.046

GERP RS

-1.1

Varity_R

0.033

gMVP

0.10

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