Variant 1-23509872-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004091.4(E2F2):c.*8T>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 0.482 in 1,524,892 control chromosomes in the GnomAD database, including 184,801 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 0.40 ( 14380 hom., cov: 32)

Exomes 𝑓: 0.49 ( 170421 hom. )

Consequence

E2F2
NM_004091.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.584

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
E2F2	NM_004091.4 linkuse as main transcript	c.*8T>C		3_prime_UTR_variant	7/7	ENST00000361729.3	NP_004082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
E2F2	ENST00000361729.3 linkuse as main transcript	c.*8T>C		3_prime_UTR_variant	7/7	1	NM_004091.4	ENSP00000355249	P1

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60329

AN:

151926

Hom.:

14387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.601

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.419

GnomAD3 exomes

AF:

0.455

AC:

82192

AN:

180532

Hom.:

20264

AF XY:

0.461

AC XY:

44009

AN XY:

95492

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.511

Gnomad EAS exome

AF:

0.589

Gnomad SAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.574

Gnomad NFE exome

AF:

0.511

Gnomad OTH exome

AF:

0.485

GnomAD4 exome

AF:

0.491

AC:

674608

AN:

1372846

Hom.:

170421

Cov.:

AF XY:

0.489

AC XY:

329317

AN XY:

673136

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.370

Gnomad4 ASJ exome

AF:

0.512

Gnomad4 EAS exome

AF:

0.603

Gnomad4 SAS exome

AF:

0.353

Gnomad4 FIN exome

AF:

0.577

Gnomad4 NFE exome

AF:

0.510

Gnomad4 OTH exome

AF:

0.468

GnomAD4 genome

AF:

0.397

AC:

60318

AN:

152046

Hom.:

14380

Cov.:

AF XY:

0.399

AC XY:

29663

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.387

Gnomad4 ASJ

AF:

0.516

Gnomad4 EAS

AF:

0.593

Gnomad4 SAS

AF:

0.337

Gnomad4 FIN

AF:

0.580

Gnomad4 NFE

AF:

0.517

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.476

Hom.:

27225

Bravo

AF:

0.375

Asia WGS

AF:

0.400

AC:

1389

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.68

DANN

Benign

0.24

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over