2-11450047-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 13/21 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

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.44
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]

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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=0.23795542).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
E2F6NM_198256.4 linkc.616G>A p.Ala206Thr missense_variant Exon 5 of 7 ENST00000381525.8 NP_937987.2 O75461-1A0A0S2Z3K8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
E2F6ENST00000381525.8 linkc.616G>A p.Ala206Thr missense_variant Exon 5 of 7 1 NM_198256.4 ENSP00000370936.3 O75461-1

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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.616G>A (p.A206T) alteration is located in exon 5 (coding exon 5) of the E2F6 gene. This alteration results from a G to A substitution at nucleotide position 616, causing the alanine (A) at amino acid position 206 to be replaced by a threonine (T). 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
0.13
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;D;.;D
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.24
T;T;T;T
MetaSVM
Benign
-0.38
T
MutationAssessor
Benign
1.4
L;.;.;.
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.42
N;N;N;N
REVEL
Benign
0.28
Sift
Benign
0.068
T;T;T;T
Sift4G
Benign
0.15
T;T;T;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-11590173; API