4-77164408-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004354.3(CCNG2):​c.840C>T​(p.Leu280Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,614,042 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 22 hom., cov: 32)
Exomes 𝑓: 0.00087 ( 15 hom. )

Consequence

CCNG2
NM_004354.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.622
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 4-77164408-C-T is Benign according to our data. Variant chr4-77164408-C-T is described in ClinVar as [Benign]. Clinvar id is 708394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.622 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00853 (1298/152190) while in subpopulation AFR AF= 0.0298 (1237/41496). AF 95% confidence interval is 0.0284. There are 22 homozygotes in gnomad4. There are 598 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1298 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCNG2NM_004354.3 linkc.840C>T p.Leu280Leu synonymous_variant Exon 7 of 8 ENST00000316355.10 NP_004345.1 Q16589-1A0A024RDC7
CCNG2XM_011532398.2 linkc.840C>T p.Leu280Leu synonymous_variant Exon 7 of 8 XP_011530700.1 Q16589-1A0A024RDC7
CCNG2XM_011532399.3 linkc.840C>T p.Leu280Leu synonymous_variant Exon 7 of 8 XP_011530701.1 Q16589-1A0A024RDC7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCNG2ENST00000316355.10 linkc.840C>T p.Leu280Leu synonymous_variant Exon 7 of 8 1 NM_004354.3 ENSP00000315743.5 Q16589-1

Frequencies

GnomAD3 genomes
AF:
0.00850
AC:
1293
AN:
152072
Hom.:
21
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0298
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00210
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:
0.000221
Gnomad OTH
AF:
0.00670
GnomAD3 exomes
AF:
0.00208
AC:
522
AN:
251432
Hom.:
8
AF XY:
0.00159
AC XY:
216
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.0291
Gnomad AMR exome
AF:
0.000925
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000967
Gnomad OTH exome
AF:
0.000651
GnomAD4 exome
AF:
0.000867
AC:
1267
AN:
1461852
Hom.:
15
Cov.:
31
AF XY:
0.000737
AC XY:
536
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.0311
Gnomad4 AMR exome
AF:
0.00112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000927
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000791
Gnomad4 OTH exome
AF:
0.00121
GnomAD4 genome
AF:
0.00853
AC:
1298
AN:
152190
Hom.:
22
Cov.:
32
AF XY:
0.00804
AC XY:
598
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.0298
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.00663
Alfa
AF:
0.00276
Hom.:
5
Bravo
AF:
0.00912
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Oct 10, 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
BayesDel_noAF
Benign
-0.39
CADD
Benign
6.4
DANN
Benign
0.77
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs4150086; hg19: chr4-78085561; API