Genetic Variant E2F7:p.Lys651Asn (chr12-77028070-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203394.3(E2F7):c.1953A>T(p.Lys651Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

E2F7
NM_203394.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.098784834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F7	NM_203394.3 link	c.1953A>T	p.Lys651Asn	missense_variant	Exon 11 of 13	ENST00000322886.12	NP_976328.2	Q96AV8-1
E2F7	XM_011537966.3 link	c.1818A>T	p.Lys606Asn	missense_variant	Exon 10 of 12		XP_011536268.1
E2F7	XM_011537969.3 link	c.1650A>T	p.Lys550Asn	missense_variant	Exon 10 of 12		XP_011536271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
E2F7	ENST00000322886.12 link	c.1953A>T	p.Lys651Asn	missense_variant	Exon 11 of 13	1	NM_203394.3	ENSP00000323246.7	Q96AV8-1
E2F7	ENST00000550669.5 link	c.1953A>T	p.Lys651Asn	missense_variant	Exon 11 of 11	1		ENSP00000448245.1	F8VSE7
E2F7	ENST00000416496.6 link	c.1953A>T	p.Lys651Asn	missense_variant	Exon 11 of 12	5		ENSP00000393639.2	Q96AV8-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1953A>T (p.K651N) alteration is located in exon 11 (coding exon 10) of the E2F7 gene. This alteration results from a A to T substitution at nucleotide position 1953, causing the lysine (K) at amino acid position 651 to be replaced by an asparagine (N). 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

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

T;.;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.099

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.42

N;N;N

REVEL

Benign

0.023

Sift

Uncertain

0.023

D;D;D

Sift4G

Benign

0.11

T;T;T

Polyphen

0.020

B;B;.

Vest4

0.25

MutPred

0.39

Gain of catalytic residue at D652 (P = 9e-04);Gain of catalytic residue at D652 (P = 9e-04);Gain of catalytic residue at D652 (P = 9e-04);

MVP

0.21

MPC

0.35

ClinPred

0.22

GERP RS

3.1

Varity_R

0.072

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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