chr11-86245325-C-A

Variant names:

• chr11-86245325-C-A
• rs779705890
• NM_003797.5:c.96C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_003797.5(EED):​c.96C>A​(p.Asp32Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,440 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D32D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EED NM_003797.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.824
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Cohen-Gibson syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Weaver syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 10 curated pathogenic missense variants (we use a threshold of 10). The gene has 3 curated benign missense variants. Gene score misZ: 2.7345 (below the threshold of 3.09). Trascript score misZ: 2.9199 (below the threshold of 3.09). GenCC associations: The gene is linked to Cohen-Gibson syndrome, Weaver syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.122766405).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003797.5. 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
	EED	NM_003797.5	MANE Select	c.96C>A	p.Asp32Glu	missense	Exon 1 of 12	NP_003788.2
	EED	NM_001308007.2		c.96C>A	p.Asp32Glu	missense	Exon 1 of 13	NP_001294936.1	O75530-2
	EED	NM_001440587.1		c.96C>A	p.Asp32Glu	missense	Exon 1 of 12	NP_001427516.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EED	ENST00000263360.11	TSL:1 MANE Select	c.96C>A	p.Asp32Glu	missense	Exon 1 of 12	ENSP00000263360.6	O75530-1
	EED	ENST00000351625.10	TSL:1	c.96C>A	p.Asp32Glu	missense	Exon 1 of 13	ENSP00000338186.5	O75530-2
	EED	ENST00000327320.8	TSL:1	c.96C>A	p.Asp32Glu	missense	Exon 1 of 11	ENSP00000315587.4	O75530-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460440 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726476

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111226

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.025
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.82
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.22
Sift	Benign	0.46	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.30		Gain of glycosylation at S34 (P = 0.1204)
MVP		0.44
MPC		0.0015
ClinPred		0.39	T
GERP RS		3.8
PromoterAI		-0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.31
Mutation Taster		=88/12	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

dbSNP: rs779705890; hg19: chr11-85956367;