chr4-77158566-C-G

Position:

• chr4-77158566-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004354.3(CCNG2):​c.34C>G​(p.His12Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: CCNG2 NM_004354.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81

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 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=0.06144333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNG2	NM_004354.3	c.34C>G	p.His12Asp	missense_variant	2/8	ENST00000316355.10	NP_004345.1
CCNG2	XM_011532398.2	c.34C>G	p.His12Asp	missense_variant	2/8		XP_011530700.1
CCNG2	XM_011532399.3	c.34C>G	p.His12Asp	missense_variant	2/8		XP_011530701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNG2	ENST00000316355.10	c.34C>G	p.His12Asp	missense_variant	2/8	1	NM_004354.3	ENSP00000315743.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 17, 2023

The c.34C>G (p.H12D) alteration is located in exon 2 (coding exon 1) of the CCNG2 gene. This alteration results from a C to G substitution at nucleotide position 34, causing the histidine (H) at amino acid position 12 to be replaced by an aspartic acid (D). 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	0.064
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.82
DEOGEN2	Benign	0.071	T;T;T;.;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.31	.;.;T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.061	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N;N;N;.;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.66	N;N;N;N;N
REVEL	Benign	0.015
Sift	Benign	0.72	T;T;T;T;T
Sift4G	Benign	0.73	T;T;T;T;T
Polyphen		0.0010	B;B;B;.;.
Vest4		0.18
MutPred		0.39		Gain of catalytic residue at H12 (P = 0.0455);Gain of catalytic residue at H12 (P = 0.0455);Gain of catalytic residue at H12 (P = 0.0455);Gain of catalytic residue at H12 (P = 0.0455);Gain of catalytic residue at H12 (P = 0.0455);
MVP		0.29
MPC		0.32
ClinPred		0.050	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
gMVP		0.46

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: chr4-78079719;