Genetic Variant CCNI2:p.Thr82Lys (chr5-132747740-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039780.4(CCNI2):c.245C>A(p.Thr82Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,316,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. T82M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CCNI2
NM_001039780.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0600

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09367964).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039780.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNI2	NM_001039780.4	MANE Select	c.245C>A	p.Thr82Lys	missense	Exon 1 of 6	NP_001034869.1	Q6ZMN8-1
CCNI2	NM_001287252.2		c.245C>A	p.Thr82Lys	missense	Exon 1 of 6	NP_001274181.1	Q6ZMN8-2
CCNI2	NM_001287253.2		c.245C>A	p.Thr82Lys	missense	Exon 1 of 6	NP_001274182.1	Q6ZMN8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNI2	ENST00000378731.6	TSL:1 MANE Select	c.245C>A	p.Thr82Lys	missense	Exon 1 of 6	ENSP00000368005.1	Q6ZMN8-1
CCNI2	ENST00000614847.1	TSL:1	c.245C>A	p.Thr82Lys	missense	Exon 1 of 6	ENSP00000478257.1	Q6ZMN8-2
CCNI2	ENST00000878149.1		c.245C>A	p.Thr82Lys	missense	Exon 1 of 6	ENSP00000548208.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000152

AC:

AN:

1316768

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

648434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26610

American (AMR)

AF:

0.0000402

AC:

AN:

24894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22426

East Asian (EAS)

AF:

0.0000338

AC:

AN:

29576

South Asian (SAS)

AF:

0.00

AC:

AN:

71018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3888

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1050816

Other (OTH)

AF:

0.00

AC:

AN:

54738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.35

M_CAP

Benign

0.0042

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.060

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.80

REVEL

Benign

0.028

Sift

Benign

0.21

Sift4G

Benign

0.63

Polyphen

0.16

Vest4

0.098

MutPred

0.23

Loss of phosphorylation at T82 (P = 0.0059)

MVP

0.081

MPC

1.5

ClinPred

0.16

GERP RS

0.88

PromoterAI

0.018

Neutral

(source)

Varity_R

0.096

gMVP

0.17

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over