Variant chr4-77160839-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004354.3(CCNG2):c.395A>G(p.Lys132Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000151 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.000015 ( 0 hom. )

Consequence

CCNG2
NM_004354.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74

Variant links:

Genes affected

CCNG2 (HGNC:1593): (cyclin G2) The eukaryotic cell cycle is governed by cyclin-dependent protein kinases (CDKs) whose activities are regulated by cyclins and CDK inhibitors. The 8 species of cyclins reported in mammals, cyclins A through H, share a conserved amino acid sequence of about 90 residues called the cyclin box. The amino acid sequence of cyclin G is well conserved among mammals. The nucleotide sequence of cyclin G1 and cyclin G2 are 53% identical. Unlike cyclin G1, cyclin G2 contains a C-terminal PEST protein destabilization motif, suggesting that cyclin G2 expression is tightly regulated through the cell cycle. [provided by RefSeq, Jul 2008]

CCNG2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20304957).

BS2

High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNG2	NM_004354.3 link	c.395A>G	p.Lys132Arg	missense_variant	4/8	ENST00000316355.10	NP_004345.1	Q16589-1A0A024RDC7
CCNG2	XM_011532398.2 link	c.395A>G	p.Lys132Arg	missense_variant	4/8		XP_011530700.1	Q16589-1A0A024RDC7
CCNG2	XM_011532399.3 link	c.395A>G	p.Lys132Arg	missense_variant	4/8		XP_011530701.1	Q16589-1A0A024RDC7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNG2	ENST00000316355.10 link	c.395A>G	p.Lys132Arg	missense_variant	4/8	1	NM_004354.3	ENSP00000315743.5		Q16589-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251394

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727190

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:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Feb 07, 2023

The c.395A>G (p.K132R) alteration is located in exon 4 (coding exon 3) of the CCNG2 gene. This alteration results from a A to G substitution at nucleotide position 395, causing the lysine (K) at amino acid position 132 to be replaced by an arginine (R). 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

0.078

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

T;T;T;.;.

Eigen

Benign

-0.015

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

.;.;D;T;D

M_CAP

Benign

0.0046

MetaRNN

Benign

0.20

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

L;L;L;.;L

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.12

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.77

T;T;T;T;T

Sift4G

Benign

0.67

T;T;T;T;T

Polyphen

0.60

P;P;P;.;.

Vest4

0.091

MutPred

0.41

Loss of methylation at K132 (P = 0.0012);Loss of methylation at K132 (P = 0.0012);Loss of methylation at K132 (P = 0.0012);Loss of methylation at K132 (P = 0.0012);Loss of methylation at K132 (P = 0.0012);

MVP

0.46

MPC

0.25

ClinPred

0.21

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.10

gMVP

0.15

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