rs193921146
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5
The NM_004456.5(EZH2):c.457_459del(p.Tyr153del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
EZH2
NM_004456.5 inframe_deletion
NM_004456.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.98
Genes affected
EZH2 (HGNC:3527): (enhancer of zeste 2 polycomb repressive complex 2 subunit) 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 associates with the embryonic ectoderm development protein, the VAV1 oncoprotein, and the X-linked nuclear protein. This protein may play a role in the hematopoietic and central nervous systems. Multiple alternatively splcied transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a turn (size 2) in uniprot entity EZH2_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_004456.5
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_004456.5. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 7-148829752-CATA-C is Pathogenic according to our data. Variant chr7-148829752-CATA-C is described in ClinVar as [Pathogenic]. Clinvar id is 30198.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-148829752-CATA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EZH2 | NM_004456.5 | c.457_459del | p.Tyr153del | inframe_deletion | 5/20 | ENST00000320356.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EZH2 | ENST00000320356.7 | c.457_459del | p.Tyr153del | inframe_deletion | 5/20 | 1 | NM_004456.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Weaver syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 13, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at