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

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

14 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High AC in GnomAd4 at 1067 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004091.4. 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
	E2F2	NM_004091.4	MANE Select	c.613G>A	p.Gly205Arg	missense	Exon 4 of 7	NP_004082.1	Q14209

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F2	ENST00000361729.3	TSL:1 MANE Select	c.613G>A	p.Gly205Arg	missense	Exon 4 of 7	ENSP00000355249.2	Q14209
	E2F2	ENST00000915331.1		c.607G>A	p.Gly203Arg	missense	Exon 4 of 7	ENSP00000585390.1

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

GnomAD2 exomes

AF:

0.00737

AC:

1845

AN:

250308

AF XY:

0.00788

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 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

African (AFR)

AF:

0.00129

AC:

AN:

33434

American (AMR)

AF:

0.00246

AC:

110

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00483

AC:

126

AN:

26104

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39610

South Asian (SAS)

AF:

0.0134

AC:

1155

AN:

86158

European-Finnish (FIN)

AF:

0.00202

AC:

108

AN:

53406

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0113

AC:

12575

AN:

1111654

Other (OTH)

AF:

0.00863

AC:

521

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

799

1599

2398

3198

3997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

480

960

1440

1920

2400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00700

AC:

1067

AN:

152328

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

464

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00188

AC:

AN:

41570

American (AMR)

AF:

0.00314

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00662

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.0141

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0119

AC:

811

AN:

68032

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

116

173

231

289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00983

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

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

PhyloP100

0.81

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

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over