4-77158615-A-G

Variant names:

• chr4-77158615-A-G
• rs4150051
• NM_004354.3:c.83A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004354.3(CCNG2):​c.83A>G​(p.Glu28Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000804 in 1,614,128 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.0044 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00043 (3 hom.)
• Consequence: CCNG2 NM_004354.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.39

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0073105395).
• BP6: Variant 4-77158615-A-G is Benign according to our data. Variant chr4-77158615-A-G is described in ClinVar as [Benign]. Clinvar id is 708768.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 674 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNG2	NM_004354.3	c.83A>G	p.Glu28Gly	missense_variant	Exon 2 of 8	ENST00000316355.10	NP_004345.1
CCNG2	XM_011532398.2	c.83A>G	p.Glu28Gly	missense_variant	Exon 2 of 8		XP_011530700.1
CCNG2	XM_011532399.3	c.83A>G	p.Glu28Gly	missense_variant	Exon 2 of 8		XP_011530701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNG2	ENST00000316355.10	c.83A>G	p.Glu28Gly	missense_variant	Exon 2 of 8	1	NM_004354.3	ENSP00000315743.5

Frequencies

GnomAD3 genomes AF: 0.00444 AC: 675 AN: 152130 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00115 AC: 290 AN: 251494 Hom.: 3 AF XY: 0.000831 AC XY: 113 AN XY: 135920

Gnomad AFR exome AF: 0.0165

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000427 AC: 624 AN: 1461880 Hom.: 3 Cov.: 31 AF XY: 0.000347 AC XY: 252 AN XY: 727244

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000198

Gnomad4 OTH exome AF: 0.000861

GnomAD4 genome AF: 0.00443 AC: 674 AN: 152248 Hom.: 8 Cov.: 33 AF XY: 0.00426 AC XY: 317 AN XY: 74436

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000839 Hom.: 1

Bravo AF: 0.00515

ESP6500AA AF: 0.0152 AC: 67

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00146 AC: 177

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.67	D;D;D;.;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	.;.;D;D;D
MetaRNN	Benign	0.0073	T;T;T;T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	2.9	M;M;M;.;M
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.5	D;D;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D
Polyphen		1.0	D;D;D;.;.
Vest4		0.68
MVP		0.54
MPC		0.94
ClinPred		0.052	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.50
gMVP		0.91

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

Other links and lift over

dbSNP: rs4150051; hg19: chr4-78079768;