1-23521045-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004091.4(E2F2):c.605C>T(p.Thr202Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,613,178 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 20 hom. )

Consequence

E2F2
NM_004091.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.32

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036780536).

BP6

Variant 1-23521045-G-A is Benign according to our data. Variant chr1-23521045-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 713748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00423 (6185/1460840) while in subpopulation MID AF = 0.0239 (137/5744). AF 95% confidence interval is 0.0206. There are 20 homozygotes in GnomAdExome4. There are 3063 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 468 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F2	NM_004091.4 link	c.605C>T	p.Thr202Ile	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.605C>T	p.Thr202Ile	missense_variant	Exon 4 of 7	1	NM_004091.4	ENSP00000355249.2		Q14209

Frequencies

GnomAD3 genomes

AF:

0.00307

AC:

468

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00582

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00447

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00322

AC:

804

AN:

249764

AF XY:

0.00320

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.00470

Gnomad ASJ exome

AF:

0.00210

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00462

Gnomad OTH exome

AF:

0.00706

GnomAD4 exome

AF:

0.00423

AC:

6185

AN:

1460840

Hom.:

Cov.:

AF XY:

0.00421

AC XY:

3063

AN XY:

726704

show subpopulations

Gnomad4 AFR exome

AF:

0.00156

AC:

AN:

33408

Gnomad4 AMR exome

AF:

0.00451

AC:

201

AN:

44610

Gnomad4 ASJ exome

AF:

0.00134

AC:

AN:

26084

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39602

Gnomad4 SAS exome

AF:

0.00139

AC:

120

AN:

86118

Gnomad4 FIN exome

AF:

0.000262

AC:

AN:

53390

Gnomad4 NFE exome

AF:

0.00480

AC:

5336

AN:

1111534

Gnomad4 Remaining exome

AF:

0.00481

AC:

290

AN:

60350

Heterozygous variant carriers

345

690

1034

1379

1724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<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:

0.00307

AC:

468

AN:

152338

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

199

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000938

AC:

0.000937816

AN:

0.000937816

Gnomad4 AMR

AF:

0.00581

AC:

0.00581471

AN:

0.00581471

Gnomad4 ASJ

AF:

0.00173

AC:

0.00172811

AN:

0.00172811

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00186

AC:

0.0018649

AN:

0.0018649

Gnomad4 FIN

AF:

0.0000942

AC:

0.000094162

AN:

0.000094162

Gnomad4 NFE

AF:

0.00447

AC:

0.00446849

AN:

0.00446849

Gnomad4 OTH

AF:

0.00710

AC:

0.00710227

AN:

0.00710227

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.00420

Hom.:

Bravo

AF:

0.00314

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00288

AC:

350

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00546

EpiControl

AF:

0.00566

ClinVar

Significance: Likely 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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.43

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.0037

MetaSVM

Uncertain

0.37

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

REVEL

Benign

0.26

Sift

Benign

0.11

Sift4G

Benign

0.17

Polyphen

0.97

Vest4

0.055

MVP

0.62

MPC

0.40

ClinPred

0.023

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.039

gMVP

0.19

Mutation Taster

=93/7

polymorphism

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over