Variant 12-77027999-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000322886.12(E2F7):c.2024T>A(p.Val675Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,614,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V675V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

E2F7
ENST00000322886.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.164

Variant links:

Genes affected

E2F7 (HGNC:23820): (E2F transcription factor 7) Enables DNA-binding transcription factor activity; cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Involved in several processes, including DNA damage response, signal transduction by p53 class mediator; regulation of transcription, DNA-templated; and sprouting angiogenesis. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

E2F7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011700869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
E2F7	NM_203394.3 linkuse as main transcript	c.2024T>A	p.Val675Asp	missense_variant	11/13	ENST00000322886.12	NP_976328.2
E2F7	XM_011537966.3 linkuse as main transcript	c.1889T>A	p.Val630Asp	missense_variant	10/12		XP_011536268.1
E2F7	XM_011537969.3 linkuse as main transcript	c.1721T>A	p.Val574Asp	missense_variant	10/12		XP_011536271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
E2F7	ENST00000322886.12 linkuse as main transcript	c.2024T>A	p.Val675Asp	missense_variant	11/13	1	NM_203394.3	ENSP00000323246	P1	Q96AV8-1
E2F7	ENST00000550669.5 linkuse as main transcript	c.2024T>A	p.Val675Asp	missense_variant	11/11	1		ENSP00000448245
E2F7	ENST00000416496.6 linkuse as main transcript	c.2024T>A	p.Val675Asp	missense_variant	11/12	5		ENSP00000393639		Q96AV8-2

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251460

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000427

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000544

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2022

The c.2024T>A (p.V675D) alteration is located in exon 11 (coding exon 10) of the E2F7 gene. This alteration results from a T to A substitution at nucleotide position 2024, causing the valine (V) at amino acid position 675 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.5

DANN

Benign

0.79

DEOGEN2

Benign

0.073

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.83

N;N;N

REVEL

Benign

0.038

Sift

Benign

0.36

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.094

MVP

0.20

MPC

0.48

ClinPred

0.0074

GERP RS

-3.0

Varity_R

0.059

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over