4-77161493-AGC-CGG

Variant names:

• chr4-77161493-AGC-CGG
• NM_004354.3:c.541_543delAGCinsCGG
• CCNG2 p.Ser181Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004354.3(CCNG2):​c.541_543delAGCinsCGG​(p.Ser181Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCNG2 NM_004354.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.83
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004354.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNG2	NM_004354.3	MANE Select	c.541_543delAGCinsCGG	p.Ser181Arg	missense	N/A	NP_004345.1	Q16589-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNG2	ENST00000316355.10	TSL:1 MANE Select	c.541_543delAGCinsCGG	p.Ser181Arg	missense	N/A	ENSP00000315743.5	Q16589-1
	CCNG2	ENST00000395640.5	TSL:1	c.541_543delAGCinsCGG	p.Ser181Arg	missense	N/A	ENSP00000379002.1	Q16589-1
	CCNG2	ENST00000497512.5	TSL:1	n.823_825delAGCinsCGG		non_coding_transcript_exon	Exon 5 of 12

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-78082646;