1-23521479-T-C

Variant names:

• chr1-23521479-T-C
• rs2038026
• NM_004091.4:c.578+358A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.93).
• 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 rank	MANE	Protein	UniProt
E2F2	NM_004091.4	c.578+358A>G		intron_variant	Intron 3 of 6	ENST00000361729.3	NP_004082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F2	ENST00000361729.3	c.578+358A>G		intron_variant	Intron 3 of 6	1	NM_004091.4	ENSP00000355249.2

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

African (AFR) AF: 0.122 AC: 1761 AN: 14442

American (AMR) AF: 0.509 AC: 461 AN: 906

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 2515 AN: 4808

East Asian (EAS) AF: 0.827 AC: 2760 AN: 3336

South Asian (SAS) AF: 0.629 AC: 9533 AN: 15154

European-Finnish (FIN) AF: 0.699 AC: 172 AN: 246

Middle Eastern (MID) AF: 0.489 AC: 729 AN: 1492

European-Non Finnish (NFE) AF: 0.538 AC: 378340 AN: 702942

Other (OTH) AF: 0.534 AC: 13447 AN: 25178

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

African (AFR) AF: 0.163 AC: 6740 AN: 41442

American (AMR) AF: 0.482 AC: 7352 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1821 AN: 3464

East Asian (EAS) AF: 0.848 AC: 4363 AN: 5148

South Asian (SAS) AF: 0.641 AC: 3082 AN: 4810

European-Finnish (FIN) AF: 0.680 AC: 7180 AN: 10562

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37366 AN: 67944

Other (OTH) AF: 0.465 AC: 982 AN: 2110

Alfa AF: 0.507 Hom.: 4337

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
PhyloP100		-0.25
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: rs2038026; hg19: chr1-23847971; COSMIC: COSV62276326; COSMIC: COSV62276326;