dbSNP rs2229297: E2F2:p.Gly205Arg (chr1-23521037-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004091.4(E2F2):c.613G>A(p.Gly205Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00978 in 1,613,476 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 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 Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0070 ( 10 hom., cov: 32)

Exomes 𝑓: 0.010 ( 91 hom. )

Consequence

E2F2
NM_004091.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.807

Variant links:

Genes affected

E2F2 (HGNC:3114): (E2F transcription factor 2) The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F1 and E2F3, have an additional cyclin binding domain. This protein binds specifically to retinoblastoma protein pRB in a cell-cycle dependent manner, and it exhibits overall 46% amino acid identity to E2F1. [provided by RefSeq, Jul 2008]

E2F2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004575819).

BS2

High AC in GnomAd4 at 1067 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F2	NM_004091.4 link	c.613G>A	p.Gly205Arg	missense_variant	Exon 4 of 7	ENST00000361729.3	NP_004082.1	Q14209

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F2	ENST00000361729.3 link	c.613G>A	p.Gly205Arg	missense_variant	Exon 4 of 7	1	NM_004091.4	ENSP00000355249.2		Q14209

Frequencies

GnomAD3 genomes

AF:

0.00702

AC:

1068

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00737

AC:

1845

AN:

250308

Hom.:

AF XY:

0.00788

AC XY:

1067

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00230

Gnomad ASJ exome

AF:

0.00458

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.0139

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.00770

GnomAD4 exome

AF:

0.0101

AC:

14705

AN:

1461148

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

7546

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.00246

Gnomad4 ASJ exome

AF:

0.00483

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0134

Gnomad4 FIN exome

AF:

0.00202

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.00863

GnomAD4 genome

AF:

0.00700

AC:

1067

AN:

152328

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

464

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00665

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0124

AC:

107

ExAC

AF:

0.00789

AC:

958

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.00981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.097

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.28

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.3

REVEL

Benign

0.068

Sift

Benign

0.13

Sift4G

Benign

0.42

Polyphen

0.0070

Vest4

0.12

MutPred

0.10

Gain of solvent accessibility (P = 0.0306);

MVP

0.22

MPC

0.39

ClinPred

0.0028

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over