dbSNP rs79101220: CCNT2:p.Ile320Val (chr2-134953413-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_058241.3(CCNT2):c.958A>G(p.Ile320Val) 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 1,607,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CCNT2
NM_058241.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Publications

1 publications found

Variant links:

Genes affected

CCNT2 (HGNC:1600): (cyclin T2) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. The p-TEFb complex containing this cyclin was reported to interact with, and act as a negative regulator of human immunodeficiency virus type 1 (HIV-1) Tat protein. A pseudogene of this gene is found on chromosome 1. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Dec 2010]

CCNT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011051208).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058241.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNT2	NM_058241.3	MANE Select	c.958A>G	p.Ile320Val	missense	Exon 9 of 9	NP_490595.1	O60583-1
CCNT2	NM_001241.4		c.958A>G	p.Ile320Val	missense	Exon 9 of 10	NP_001232.1	O60583-2
CCNT2	NM_001320748.2		c.526A>G	p.Ile176Val	missense	Exon 10 of 10	NP_001307677.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNT2	ENST00000264157.10	TSL:1 MANE Select	c.958A>G	p.Ile320Val	missense	Exon 9 of 9	ENSP00000264157.5	O60583-1
CCNT2	ENST00000295238.11	TSL:1	c.958A>G	p.Ile320Val	missense	Exon 9 of 10	ENSP00000295238.6	O60583-2
CCNT2	ENST00000419781.5	TSL:1	n.*842A>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000404653.1	F2Z2C9

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

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

GnomAD2 exomes

AF:

0.0000755

AC:

AN:

238482

AF XY:

0.0000542

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000998

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000945

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1455112

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

723562

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32978

American (AMR)

AF:

0.00

AC:

AN:

44078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.000385

AC:

AN:

38982

South Asian (SAS)

AF:

0.00

AC:

AN:

85384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108494

Other (OTH)

AF:

0.0000333

AC:

AN:

60114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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

AF:

0.0000460

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00135

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000660

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.075

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.73

M_CAP

Benign

0.0024

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

2.3

PrimateAI

Benign

0.35

PROVEAN

Benign

0.040

REVEL

Benign

0.10

Sift

Benign

0.32

Sift4G

Benign

0.51

Polyphen

0.0050

Vest4

0.099

MutPred

0.099

Gain of glycosylation at S325 (P = 0.1656)

MVP

0.38

MPC

0.088

ClinPred

0.020

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.18

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over