rs3218211

Positions:

• chr1-23509302-A-G
• chr1-23509302-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
E2F2	NM_004091.4	c.*578T>C		3_prime_UTR_variant	7/7	ENST00000361729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
E2F2	ENST00000361729.3	c.*578T>C		3_prime_UTR_variant	7/7	1	NM_004091.4	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72458 AN: 151854 Hom.: 17661 Cov.: 31

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: 28 AN: 72 Hom.: 4 Cov.: 0 AF XY: 0.405 AC XY: 17 AN XY: 42

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.477 AC: 72477 AN: 151972 Hom.: 17656 Cov.: 31 AF XY: 0.476 AC XY: 35344 AN XY: 74268

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.468

Alfa AF: 0.499 Hom.: 3504

Bravo AF: 0.465

Asia WGS AF: 0.426 AC: 1479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.51

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

Other links and lift over

dbSNP: rs3218211; hg19: chr1-23835794; COSMIC: COSV62276307;