Variant chr2-134953258-T-C 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_058241.3(CCNT2):c.803T>C(p.Val268Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000823 in 1,458,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CCNT2
NM_058241.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

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:

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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=0.029317617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCNT2	NM_058241.3 linkuse as main transcript	c.803T>C	p.Val268Ala	missense_variant	9/9	ENST00000264157.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNT2	ENST00000264157.10 linkuse as main transcript	c.803T>C	p.Val268Ala	missense_variant	9/9	1	NM_058241.3	P4	O60583-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

249530

Hom.:

AF XY:

0.0000593

AC XY:

AN XY:

135008

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1458964

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

725132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000278

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

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

Mar 29, 2024

The c.803T>C (p.V268A) alteration is located in exon 9 (coding exon 9) of the CCNT2 gene. This alteration results from a T to C substitution at nucleotide position 803, causing the valine (V) at amino acid position 268 to be replaced by an alanine (A). 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

0.068

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.51

DEOGEN2

Benign

0.067

.;.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

.;N;N

MutationTaster

Benign

0.58

D;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.13

N;N;N

REVEL

Benign

0.049

Sift

Benign

0.76

T;T;T

Sift4G

Benign

0.76

T;T;T

Polyphen

0.0020, 0.0010

.;B;B

Vest4

0.10, 0.037

MutPred

0.30

.;Loss of ubiquitination at K265 (P = 0.0607);Loss of ubiquitination at K265 (P = 0.0607);

MVP

0.47

MPC

1.5

ClinPred

0.028

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.059

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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