dbSNP rs3218211: E2F2:c.*578T>C (chr1-23509302-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.*578T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,044 control chromosomes in the GnomAD database, including 17,660 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 0.48 ( 17656 hom., cov: 31)

Exomes 𝑓: 0.39 ( 4 hom. )

Consequence

E2F2
NM_004091.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

11 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

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.*578T>C		3_prime_UTR	Exon 7 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.*578T>C		3_prime_UTR	Exon 7 of 7	ENSP00000355249.2	Q14209
	E2F2	ENST00000915331.1		c.*578T>C		3_prime_UTR	Exon 7 of 7	ENSP00000585390.1

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72458

AN:

151854

Hom.:

17661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.601

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.594

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.470

GnomAD4 exome

AF:

0.389

AC:

AN:

Hom.:

Cov.:

AF XY:

0.405

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.354

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.477

AC:

72477

AN:

151972

Hom.:

17656

Cov.:

AF XY:

0.476

AC XY:

35344

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.400

AC:

16590

AN:

41470

American (AMR)

AF:

0.420

AC:

6408

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

1803

AN:

3466

East Asian (EAS)

AF:

0.593

AC:

3054

AN:

5150

South Asian (SAS)

AF:

0.338

AC:

1630

AN:

4824

European-Finnish (FIN)

AF:

0.580

AC:

6132

AN:

10566

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.518

AC:

35203

AN:

67918

Other (OTH)

AF:

0.468

AC:

986

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1881

3761

5642

7522

9403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<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:

0.497

Hom.:

6626

Bravo

AF:

0.465

Asia WGS

AF:

0.426

AC:

1479

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.5

(source)

DANN

Benign

0.51

PhyloP100

0.23

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over