chr2-11450047-C-T

Variant names:

• chr2-11450047-C-T
• NM_198256.4:c.616G>A

Variant summary

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

The NM_198256.4(E2F6):​c.616G>A​(p.Ala206Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000021 (0 hom.)
• Consequence: E2F6 NM_198256.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.44
• 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=0.23795542).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F6	NM_198256.4	MANE Select	c.616G>A	p.Ala206Thr	missense	Exon 5 of 7	NP_937987.2	O75461-1
	E2F6	NM_001278275.2		c.520G>A	p.Ala174Thr	missense	Exon 6 of 8	NP_001265204.1	O75461-3
	E2F6	NM_001278276.2		c.391G>A	p.Ala131Thr	missense	Exon 6 of 8	NP_001265205.1	O75461-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F6	ENST00000381525.8	TSL:1 MANE Select	c.616G>A	p.Ala206Thr	missense	Exon 5 of 7	ENSP00000370936.3	O75461-1
	E2F6	ENST00000307236.8	TSL:1	c.520G>A	p.Ala174Thr	missense	Exon 6 of 8	ENSP00000302159.4	O75461-3
	E2F6	ENST00000542100.5	TSL:1	c.391G>A	p.Ala131Thr	missense	Exon 7 of 9	ENSP00000446315.1	O75461-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461210 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726942

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111638

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 32

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	0.13
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.036
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.4
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.28
Sift	Benign	0.068	T
Sift4G	Benign	0.15	T
Polyphen		0.20	B
Vest4		0.32
MutPred		0.25		Gain of phosphorylation at A206 (P = 0.0406)
MVP		0.55
MPC		0.0084
ClinPred		0.47	T
GERP RS		5.8
Varity_R		0.063
gMVP		0.31
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

hg19: chr2-11590173;