dbSNP rs2038027: E2F2:c.578+287T>C (chr1-23521550-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004091.4(E2F2):c.578+287T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 984,788 control chromosomes in the GnomAD database, including 148,077 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 24045 hom., cov: 31)

Exomes 𝑓: 0.54 ( 124032 hom. )

Consequence

E2F2
NM_004091.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.113

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F2	NM_004091.4 link	c.578+287T>C		intron_variant	Intron 3 of 6	ENST00000361729.3	NP_004082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F2	ENST00000361729.3 link	c.578+287T>C		intron_variant	Intron 3 of 6	1	NM_004091.4	ENSP00000355249.2

Frequencies

GnomAD3 genomes

AF:

0.557

AC:

84521

AN:

151796

Hom.:

24042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.614

Gnomad AMR

AF:

0.521

Gnomad ASJ

AF:

0.530

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.679

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.536

GnomAD4 exome

AF:

0.545

AC:

453572

AN:

832874

Hom.:

124032

Cov.:

AF XY:

0.546

AC XY:

209824

AN XY:

384612

show subpopulations

African (AFR)

AF:

0.496

AC:

7820

AN:

15776

American (AMR)

AF:

0.535

AC:

526

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.530

AC:

2732

AN:

5152

East Asian (EAS)

AF:

0.828

AC:

3006

AN:

3630

South Asian (SAS)

AF:

0.633

AC:

10420

AN:

16454

European-Finnish (FIN)

AF:

0.699

AC:

193

AN:

276

Middle Eastern (MID)

AF:

0.515

AC:

835

AN:

1620

European-Non Finnish (NFE)

AF:

0.542

AC:

412802

AN:

761692

Other (OTH)

AF:

0.558

AC:

15238

AN:

27290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

10374

20748

31121

41495

51869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16066

32132

48198

64264

80330

<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:

0.557

AC:

84563

AN:

151914

Hom.:

24045

Cov.:

AF XY:

0.565

AC XY:

41970

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.503

AC:

20827

AN:

41408

American (AMR)

AF:

0.522

AC:

7963

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.530

AC:

1839

AN:

3468

East Asian (EAS)

AF:

0.847

AC:

4371

AN:

5160

South Asian (SAS)

AF:

0.643

AC:

3096

AN:

4818

European-Finnish (FIN)

AF:

0.679

AC:

7166

AN:

10556

Middle Eastern (MID)

AF:

0.445

AC:

130

AN:

292

European-Non Finnish (NFE)

AF:

0.552

AC:

37490

AN:

67936

Other (OTH)

AF:

0.532

AC:

1122

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1849

3697

5546

7394

9243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.550

Hom.:

99766

Bravo

AF:

0.542

Asia WGS

AF:

0.688

AC:

2392

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.3

(source)

DANN

Benign

0.54

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over