4-77161668-G-C

Position:

• chr4-77161668-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004354.3(CCNG2):​c.626G>C​(p.Cys209Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: CCNG2 NM_004354.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.74

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14395031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNG2	NM_004354.3	c.626G>C	p.Cys209Ser	missense_variant	6/8	ENST00000316355.10	NP_004345.1
CCNG2	XM_011532398.2	c.626G>C	p.Cys209Ser	missense_variant	6/8		XP_011530700.1
CCNG2	XM_011532399.3	c.626G>C	p.Cys209Ser	missense_variant	6/8		XP_011530701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNG2	ENST00000316355.10	c.626G>C	p.Cys209Ser	missense_variant	6/8	1	NM_004354.3	ENSP00000315743.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.626G>C (p.C209S) alteration is located in exon 6 (coding exon 5) of the CCNG2 gene. This alteration results from a G to C substitution at nucleotide position 626, causing the cysteine (C) at amino acid position 209 to be replaced by a serine (S). 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	0.28
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.78
DEOGEN2	Benign	0.080	T;T;T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	0.0068
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	.;.;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.15	N;N;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	1.2	N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.62	T;T;T;T
Sift4G	Benign	0.91	T;T;T;T
Polyphen		0.032	B;B;B;.
Vest4		0.46
MutPred		0.60		Loss of catalytic residue at L210 (P = 0.0125);Loss of catalytic residue at L210 (P = 0.0125);Loss of catalytic residue at L210 (P = 0.0125);Loss of catalytic residue at L210 (P = 0.0125);
MVP		0.15
MPC		0.29
ClinPred		0.75	D
GERP RS		5.4
Varity_R		0.24
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-78082821;