Genetic Variant NM_198256.4:c.296G>A (chr2-11453666-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198256.4(E2F6):c.296G>A(p.Arg99Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

E2F6
NM_198256.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

Publications

6 publications found

Variant links:

Genes affected

E2F6 (HGNC:3120): (E2F transcription factor 6) This gene encodes a member of a family of transcription factors that play a crucial role in the control of the cell cycle. The protein encoded by this gene lacks the transactivation and tumor suppressor protein association domains found in other family members, and contains a modular suppression domain that functions in the inhibition of transcription. It interacts in a complex with chromatin modifying factors. There are pseudogenes for this gene on chromosomes 22 and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

E2F6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20648682).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198256.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
E2F6	NM_198256.4	MANE Select	c.296G>A	p.Arg99Gln	missense	Exon 3 of 7	NP_937987.2	O75461-1
E2F6	NM_001278275.2		c.200G>A	p.Arg67Gln	missense	Exon 4 of 8	NP_001265204.1	O75461-3
E2F6	NM_001278276.2		c.71G>A	p.Arg24Gln	missense	Exon 4 of 8	NP_001265205.1	O75461-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
E2F6	ENST00000381525.8	TSL:1 MANE Select	c.296G>A	p.Arg99Gln	missense	Exon 3 of 7	ENSP00000370936.3	O75461-1
E2F6	ENST00000307236.8	TSL:1	c.200G>A	p.Arg67Gln	missense	Exon 4 of 8	ENSP00000302159.4	O75461-3
E2F6	ENST00000542100.5	TSL:1	c.71G>A	p.Arg24Gln	missense	Exon 5 of 9	ENSP00000446315.1	O75461-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249520

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.25

DEOGEN2

Benign

0.13

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0058

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.14

PhyloP100

1.7

PrimateAI

Benign

0.44

PROVEAN

Benign

0.76

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.38

Vest4

0.12

MutPred

0.48

Loss of MoRF binding (P = 0.0401)

MVP

0.48

MPC

1.1

ClinPred

0.050

GERP RS

4.7

Varity_R

0.053

gMVP

0.66

Mutation Taster

=68/32

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over