Variant 11-86245233-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_003797.5(EED):c.4T>C(p.Ser2Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,004 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S2S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

EED
NM_003797.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

Variant links:

Genes affected

EED (HGNC:3188): (embryonic ectoderm development) This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein interacts with enhancer of zeste 2, the cytoplasmic tail of integrin beta7, immunodeficiency virus type 1 (HIV-1) MA protein, and histone deacetylase proteins. This protein mediates repression of gene activity through histone deacetylation, and may act as a specific regulator of integrin function. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

EED links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EED	NM_003797.5 linkuse as main transcript	c.4T>C	p.Ser2Pro	missense_variant	1/12	ENST00000263360.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EED	ENST00000263360.11 linkuse as main transcript	c.4T>C	p.Ser2Pro	missense_variant	1/12	1	NM_003797.5	P1	O75530-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246910

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134090

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000551

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461004

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cohen-Gibson syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

May 17, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with EED-related conditions. This variant is present in population databases (rs745543096, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 2 of the EED protein (p.Ser2Pro). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Uncertain

-0.020

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T;.;.

Eigen

Benign

0.060

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

T;T;T;T

M_CAP

Pathogenic

0.60

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

0.0

N;.;N;N

MutationTaster

Benign

0.90

D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.70

N;N;N;N

REVEL

Uncertain

0.39

Sift

Benign

0.083

T;D;T;D

Sift4G

Uncertain

0.055

T;D;T;D

Polyphen

0.97

D;D;B;B

Vest4

0.42

MutPred

0.22

Loss of phosphorylation at S2 (P = 0.0028);Loss of phosphorylation at S2 (P = 0.0028);Loss of phosphorylation at S2 (P = 0.0028);Loss of phosphorylation at S2 (P = 0.0028);

MVP

0.88

MPC

0.0012

ClinPred

0.32

GERP RS

4.5

Varity_R

0.15

gMVP

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over