chr11-86245239-AGG-TCA

Variant names:

• chr11-86245239-AGG-TCA
• NM_003797.5:c.10_12delAGGinsTCA
• EED p.Arg4Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_003797.5(EED):​c.10_12delAGGinsTCA​(p.Arg4Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: EED NM_003797.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• 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

ENSG00000288809 (HGNC:):

ACMG classification

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

• 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.

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.10_12delAGGinsTCA	p.Arg4Ser	missense	N/A	NP_003788.2
	EED	NM_001308007.2		c.10_12delAGGinsTCA	p.Arg4Ser	missense	N/A	NP_001294936.1	O75530-2
	EED	NM_001440587.1		c.10_12delAGGinsTCA	p.Arg4Ser	missense	N/A	NP_001427516.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EED	ENST00000263360.11	TSL:1 MANE Select	c.10_12delAGGinsTCA	p.Arg4Ser	missense	N/A	ENSP00000263360.6	O75530-1
	EED	ENST00000351625.10	TSL:1	c.10_12delAGGinsTCA	p.Arg4Ser	missense	N/A	ENSP00000338186.5	O75530-2
	EED	ENST00000327320.8	TSL:1	c.10_12delAGGinsTCA	p.Arg4Ser	missense	N/A	ENSP00000315587.4	O75530-3

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-85956281;