rs2038026

Positions:

• chr1-23521479-T-C
• chr1-23521479-T-G

Variant summary

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

The NM_004091.4(E2F2):​c.578+358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 920,448 control chromosomes in the GnomAD database, including 129,964 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 0.46 (18907 hom., cov: 31)
  • Exomes 𝑓: 0.53 (111057 hom.)
• Consequence: E2F2 NM_004091.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
E2F2	NM_004091.4	c.578+358A>G		intron_variant		ENST00000361729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
E2F2	ENST00000361729.3	c.578+358A>G		intron_variant		1	NM_004091.4	P1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69569 AN: 151826 Hom.: 18914 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.533 AC: 409718 AN: 768504 Hom.: 111057 AF XY: 0.535 AC XY: 190489 AN XY: 356222

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.509

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.827

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.699

Gnomad4 NFE exome AF: 0.538

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.458 AC: 69570 AN: 151944 Hom.: 18907 Cov.: 31 AF XY: 0.470 AC XY: 34879 AN XY: 74240

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.465

Alfa AF: 0.515 Hom.: 4327

Bravo AF: 0.431

Asia WGS AF: 0.657 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.39

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: rs2038026; hg19: chr1-23847971; COSMIC: COSV62276326; COSMIC: COSV62276326;