1-23509872-A-G

Variant names:

• chr1-23509872-A-G
• rs2075993
• NM_004091.4:c.*8T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F2	NM_004091.4	MANE Select	c.*8T>C		3_prime_UTR	Exon 7 of 7	NP_004082.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F2	ENST00000361729.3	TSL:1 MANE Select	c.*8T>C		3_prime_UTR	Exon 7 of 7	ENSP00000355249.2

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60329 AN: 151926 Hom.: 14387 Cov.: 32

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

GnomAD2 exomes AF: 0.455 AC: 82192 AN: 180532 AF XY: 0.461

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 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.: 46 AF XY: 0.489 AC XY: 329317 AN XY: 673136

African (AFR) AF: 0.104 AC: 3205 AN: 30856

American (AMR) AF: 0.370 AC: 13129 AN: 35510

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 10776 AN: 21042

East Asian (EAS) AF: 0.603 AC: 21898 AN: 36322

South Asian (SAS) AF: 0.353 AC: 25642 AN: 72570

European-Finnish (FIN) AF: 0.577 AC: 29102 AN: 50400

Middle Eastern (MID) AF: 0.386 AC: 2062 AN: 5336

European-Non Finnish (NFE) AF: 0.510 AC: 542333 AN: 1064226

Other (OTH) AF: 0.468 AC: 26461 AN: 56584

GnomAD4 genome AF: 0.397 AC: 60318 AN: 152046 Hom.: 14380 Cov.: 32 AF XY: 0.399 AC XY: 29663 AN XY: 74340

African (AFR) AF: 0.123 AC: 5118 AN: 41492

American (AMR) AF: 0.387 AC: 5909 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1788 AN: 3468

East Asian (EAS) AF: 0.593 AC: 3065 AN: 5172

South Asian (SAS) AF: 0.337 AC: 1623 AN: 4816

European-Finnish (FIN) AF: 0.580 AC: 6138 AN: 10584

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35128 AN: 67938

Other (OTH) AF: 0.418 AC: 882 AN: 2112

Alfa AF: 0.473 Hom.: 30905

Bravo AF: 0.375

Asia WGS AF: 0.400 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.24
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2075993; hg19: chr1-23836364; COSMIC: COSV62276310;