Genetic Variant ENST00000542100.5:c.-208G>T (chr2-11457191-C-A) – 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 ENST00000542100.5(E2F6):c.-208G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

E2F6
ENST00000542100.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

Publications

0 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=0.102136135).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000542100.5. 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.151G>T	p.Val51Leu	missense	Exon 2 of 7	NP_937987.2	O75461-1
E2F6	NM_001278276.2		c.-208G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001265205.1	O75461-2
E2F6	NM_001278277.2		c.-208G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	NP_001265206.1	O75461-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
E2F6	ENST00000542100.5	TSL:1	c.-208G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	ENSP00000446315.1	O75461-2
E2F6	ENST00000381525.8	TSL:1 MANE Select	c.151G>T	p.Val51Leu	missense	Exon 2 of 7	ENSP00000370936.3	O75461-1
E2F6	ENST00000307236.8	TSL:1	c.55G>T	p.Val19Leu	missense	Exon 3 of 8	ENSP00000302159.4	O75461-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

247078

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704464

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32350

American (AMR)

AF:

0.00

AC:

AN:

43868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25370

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39152

South Asian (SAS)

AF:

0.00

AC:

AN:

84416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53086

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5580

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1069804

Other (OTH)

AF:

0.00

AC:

AN:

58456

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.060

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.81

M_CAP

Benign

0.060

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.69

PhyloP100

2.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.14

REVEL

Benign

0.24

Sift

Benign

0.39

Sift4G

Benign

0.47

Polyphen

0.016

Vest4

0.22

MutPred

0.29

Loss of methylation at K55 (P = 0.0953)

MVP

0.70

MPC

0.91

ClinPred

0.14

GERP RS

3.1

Varity_R

0.062

gMVP

0.41

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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