chr1-23521550-A-G

Position:

• chr1-23521550-A-G

Variant summary

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

The ENST00000361729.3(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 ENST00000361729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

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=-0.84).
• 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/exons	MANE	Protein	UniProt
E2F2	NM_004091.4	c.578+287T>C		intron_variant		ENST00000361729.3	NP_004082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
E2F2	ENST00000361729.3	c.578+287T>C		intron_variant		1	NM_004091.4	ENSP00000355249	P1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84521 AN: 151796 Hom.: 24042 Cov.: 31

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.: 31 AF XY: 0.546 AC XY: 209824 AN XY: 384612

Gnomad4 AFR exome AF: 0.496

Gnomad4 AMR exome AF: 0.535

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.828

Gnomad4 SAS exome AF: 0.633

Gnomad4 FIN exome AF: 0.699

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.557 AC: 84563 AN: 151914 Hom.: 24045 Cov.: 31 AF XY: 0.565 AC XY: 41970 AN XY: 74274

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.532

Alfa AF: 0.549 Hom.: 47898

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
DANN	Benign	0.54

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: rs2038027; hg19: chr1-23848042; COSMIC: COSV62276327; COSMIC: COSV62276327;