chr2-11457191-C-T

Variant names:

• chr2-11457191-C-T
• rs1181911208
• ENST00000542100.5:c.-208G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001278276.2(E2F6):​c.-208G>A 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 0.00000192 in 1,564,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: E2F6 NM_001278276.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12
• Publications: 0 publications found

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]

ACMG classification

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=0.14142767).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278276.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F6	NM_198256.4	MANE Select	c.151G>A	p.Val51Met	missense	Exon 2 of 7	NP_937987.2	O75461-1
	E2F6	NM_001278276.2		c.-208G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001265205.1	O75461-2
	E2F6	NM_001278277.2		c.-208G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	NP_001265206.1	O75461-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F6	ENST00000542100.5	TSL:1	c.-208G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	ENSP00000446315.1	O75461-2
	E2F6	ENST00000381525.8	TSL:1 MANE Select	c.151G>A	p.Val51Met	missense	Exon 2 of 7	ENSP00000370936.3	O75461-1
	E2F6	ENST00000307236.8	TSL:1	c.55G>A	p.Val19Met	missense	Exon 3 of 8	ENSP00000302159.4	O75461-3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152114 Hom.: 0 Cov.: 33

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412082 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 704464

African (AFR) AF: 0.00 AC: 0 AN: 32350

American (AMR) AF: 0.00 AC: 0 AN: 43868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25370

East Asian (EAS) AF: 0.00 AC: 0 AN: 39152

South Asian (SAS) AF: 0.00 AC: 0 AN: 84416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5580

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069804

Other (OTH) AF: 0.00 AC: 0 AN: 58456

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152114 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74294

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.19
Sift	Benign	0.088	T
Sift4G	Benign	0.12	T
Polyphen		0.52	P
Vest4		0.22
MutPred		0.22		Gain of MoRF binding (P = 0.0935)
MVP		0.59
MPC		1.1
ClinPred		0.26	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.35
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1181911208; hg19: chr2-11597317;