The EZH2 NM_004456.5:c.1936T>A (NP_004447.2:p.(Tyr646Asn)) missense variant could not be checked in COSMIC, and lies in a statistically significant hotspot (cancerhotspots.org). Experimental evidence: Recombinant PRC2 Y641N showed 9.01 versus 4.90 units/ng/min on dimethylated H3K27, with altered H3K27me3 in heterozygous cells. Based on available guidelines, this variant is considered to be Likely Pathogenic.
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely pathogenic classification under the recorded framework.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.EZH2 encodes the catalytic component of the Polycomb repressive complex 2 (PRC2), which helps control gene activity by adding methyl groups to histone H3 and repressing developmental genes. Abnormal EZH2 activity is associated with blood disorders, including follicular and diffuse large B-cell lymphomas, myelodysplastic syndromes, and myeloproliferative neoplasms. In cancer, EZH2 can act either as an oncogene or as a tumor suppressor, depending on the cancer type.
The recorded framework is Generic ACMG/AMP 2015 with ClinGen SVI recommendations. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
Met (strong): recombinant PRC2 Y641N showed 9.01 versus 4.90 units/ng/min on dimethylated H3K27, with altered H3K27me3 in heterozygous cells.
Met at moderate strength: Tyr646 is a statistically significant recurrent EZH2 hotspot with documented altered PRC2 activity and the variant is absent from gnomAD v2.1 and v4.1.
Met at supporting strength: the variant is absent from gnomAD v2.1 and v4.1, meeting the PM2 supporting threshold of <=0.0001.
Met at moderate strength: REVEL 0.895 meets the generic PP3 moderate threshold of >=0.773 for this missense variant.
No benign criterion marked as applied in the recorded assessment.
Likely Pathogenic: PS3 strong plus PM1 and PP3 moderate satisfy the generic ACMG/AMP combination rule, with PM2 supporting additional evidence.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1 allele counts were not recorded for this variant.
Absent from gnomAD v2.1.
Not available in gnomAD-Canada v1.0.
Recorded REVEL score: 0.895. Refer to the recorded PP3/BP4 rationale for interpretation.
A ClinVar laboratory submission summary was not recorded. ClinVar API review status: criteria provided, single submitter.
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Gain-of-function; curated oncogenicity label: Likely Oncogenic.
No COSMIC evidence statement is recorded in this case.
This variant lies in a statistically significant hotspot.
ACMG/AMP criteria under Generic ACMG/AMP 2015 with ClinGen SVI recommendations, with the data and sources behind each one.
28 criteria with recorded statuses: 4 met · 7 not met · 12 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Under generic ACMG/AMP rules, PM1 is supported at moderate strength by the EZH2 Tyr641/Y646 hotspot and functional catalytic-region evidence.
PS1 and PM5 are not assessed because the available same-residue evidence is somatic/functional and does not establish the required prior pathogenic comparator under generic ACMG/AMP criteria.
PP2 is not assessed because the required gene-level benign missense rate and validated missense-mechanism evidence are unavailable.
BP1 is not met because the available EZH2 disease context supports a missense-associated dominant-negative mechanism rather than a primarily truncating mechanism.
PS2, PM6, PP1, and BS4 are not assessed because the available evidence contains no qualifying germline proband-parent data, affected-relative segregation data, or affected-relative negative testing; available variant-specific publications are somatic oncology studies.
No VCEP covers EZH2 in this case; the supplied generic ACMG/AMP 2015 definitions govern.
PS4 was not assessed because no verified case-control counts or qualifying OR/RR with confidence interval were available.
PP4 and BP5 were not assessed because the required patient-level phenotype/family-history or alternate-molecular-basis evidence was absent.
PP5 and BP6 were not met because the exact ClinVar record has a single-submitter Oncogenic classification and no expert-panel Pathogenic/Likely pathogenic, Benign, or Likely benign classification.
The variant is missense, so PP3 and BP4 use the REVEL path only; REVEL 0.895 meets PP3 moderate but not BP4 supporting.
No criteria match.
PS3 is met at strong strength. The variant NM_004456.5:c.1936T>A, p.(Tyr646Asn), is described in the functional literature as EZH2 Y641N under an alternate five-residue numbering convention. Independent functional studies used appropriate wild-type comparators and multiple biologically relevant systems. In recombinant PRC2 methyltransferase assays, Y641N had markedly altered substrate specificity: specific activity on dimethylated H3K27 was 9.01 units/ng/min versus 4.90 for wild-type EZH2, while activity on unmethylated and monomethylated substrates was reduced. Heterozygous lymphoma cell lines and tumor samples showed increased H3K27me3, and a conditional mouse model expressing Ezh2 Y641N showed increased germinal-center formation and approximately threefold increased H3K27me3, with the phenotype eliminated by EZH2 inhibition. These concordant biochemical, cellular, tumor, and in vivo results demonstrate a reproducible alteration of EZH2/PRC2 function supportive of a damaging gain-of-function effect. This satisfies the ACMG/AMP PS3 definition, although the available evidence is not a clinical diagnostic-laboratory validation study warranting escalation beyond the strong code.
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
NP_004447.2:p.(Tyr646Asn) lies at the recurrent EZH2 Tyr641/Y646 hotspot in the catalytic SET-domain region. PMID:21078963 and PMID:21190999 document recurrent substitutions at this residue and altered PRC2 methyltransferase activity, while the Cancer Hotspots result identifies EZH2 Y646 as a statistically significant hotspot. The available population data show the queried variant absent from gnomAD v2.1 and v4.1; no benign variation evidence for this hotspot was identified. Under generic ACMG/AMP, this supports PM1 at moderate strength.
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
PM2 is met at supporting strength. NM_004456.5:c.1936T>A (EZH2 p.Tyr646Asn) is absent from gnomAD v2.1 and gnomAD v4.1, and the evidence record also reports absence from GNOMAD_V2_1_NON_CANCER and GNOMAD_V3_1_NON_CANCER. Thus the variant is absent from the available population controls, satisfying the generic PM2 supporting threshold of <=0.0001; no ancestry-specific or cohort-specific frequency is available to weaken this conclusion.
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
NM_004456.5:c.1936T>A is a missense variant, NP_004447.2:p.(Tyr646Asn), so the applicable generic computational path is REVEL only. The REVEL score is 0.895, meeting the supplied PP3 moderate threshold of >= 0.773 from the ClinGen SVI REVEL calibration (Pejaver et al. 2022, PMID:36413997). SpliceAI is not used for PP3 because splice prediction is not the governing path for this missense variant; BayesDel is not available for generic PP3/BP4 strength assignment because no generic ACMG-strength calibration is established.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.). ... Missense variant -> REVEL only. Its SpliceAI score says nothing about whether the amino-acid substitution is tolerated, so 'no predicted splice impact' is never BP4 support for a missense variant. ... PP3 (moderate): >= 0.773 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
PP5 requires a reputable source to recently report the variant as pathogenic when the underlying evidence is unavailable for independent evaluation. The exact ClinVar record is classified Oncogenic with one single-submitter, criteria-provided submission and no expert-panel submission; the available record is not an exact-variant ClinVar expert-panel Pathogenic or Likely pathogenic classification. OncoKB reports Likely Oncogenic, not the required expert-panel ClinVar classification. PP5 is not met.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
BA1 is not met. NM_004456.5:c.1936T>A (EZH2 p.Tyr646Asn) is absent from gnomAD v2.1 and gnomAD v4.1, including the reported non-cancer subsets, so no filtering allele frequency or grpmax FAF is available and the >=0.05 stand-alone benign threshold is not reached. The available ClinVar record is a single-submitter somatic oncogenic classification for neoplasm, not a germline population-frequency exception that would override the observed absence.
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
BS1 is not met. The variant is absent from gnomAD v2.1 and gnomAD v4.1, and is also reported absent from the available non-cancer subsets, so the filtering allele frequency (grpmax FAF) is not elevated and cannot exceed the generic 0.01 default. No maximum-credible-frequency calculation is needed because there is no observed population frequency to evaluate; the available data do not support a benign frequency signal.
Allele frequency is greater than expected for the disorder.
BS3 is not met because the available functional studies do not show no damaging effect on protein function or splicing; instead, they show a reproducible altered EZH2/PRC2 function. The same variant, described as EZH2 Y641N under an alternate numbering convention, displayed increased activity on dimethylated H3K27 in recombinant PRC2 assays, increased H3K27me3 in heterozygous lymphoma cells and tumors, and a gain-of-function phenotype in a conditional mouse model. No benign functional result or validated assay demonstrating preserved protein function or normal splicing was identified. Therefore BS3 is contradicted by the functional evidence rather than merely left unassessed.
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
BP1 requires a gene for which primarily truncating variants are known to cause disease. The available EZH2 germline context instead describes Weaver syndrome as associated with heterozygous missense variants and notes a lack of early truncating mutations, with a proposed dominant-negative mechanism. That evidence does not support a primarily truncating disease mechanism, so BP1 is not met.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
NM_004456.5:c.1936T>A is a missense variant, so BP4 must be judged by REVEL only. REVEL is 0.895, which does not meet the supplied BP4 supporting threshold of <= 0.29 from the ClinGen SVI REVEL calibration (Pejaver et al. 2022, PMID:36413997). The SpliceAI max delta of 0.006 cannot substitute for the missense REVEL path, and the BayesDel score is not usable because no generic ACMG-strength calibration is established.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc). ... Missense variant -> REVEL only. Its SpliceAI score says nothing about whether the amino-acid substitution is tolerated, so 'no predicted splice impact' is never BP4 support for a missense variant. ... BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
BP6 requires a reputable source to recently report the variant as benign when the underlying evidence is unavailable for independent evaluation. The exact ClinVar record is classified Oncogenic with one single-submitter, criteria-provided submission and no expert-panel submission; no exact-variant ClinVar expert-panel Benign or Likely benign classification is present. BP6 is not met.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
The variant is NP_004447.2:p.(Tyr646Asn), also reported as EZH2 Y641N under an alternate five-residue numbering convention in PMID:21078963, PMID:21190999, and PMID:23680150. These papers provide functional and somatic lymphoma evidence for the same amino-acid substitution, but the available evidence does not establish a previously established pathogenic variant under generic germline ACMG/AMP criteria; ClinVar is a single-submitter somatic Oncogenic record without an expert-panel or usable criterion-lead submission. Therefore PS1 cannot be adjudicated as met from the available evidence.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
PS2 cannot be assessed because the available evidence does not document a proband with the relevant germline disease, absence of family history, or de novo status established by confirmation of both maternity and paternity. The available literature concerns somatic EZH2 mutations in lymphoma and does not provide qualifying parental testing for this variant.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
The governing PS4 rule requires a case-control prevalence comparison with RR or OR >5.0 and a confidence interval that does not include 1.0. The reviewed variant-specific literature reports EZH2 Y641N/Y646N in lymphoma cell lines, tumors, and experimental models, but does not provide affected-case and unaffected/population-control counts or a case-control OR/RR and confidence interval. The literature_pass PS4 index points to PMID:34131312, but that paper is a general chromosomal microarray technical standard, is not available in the case full-text map, and its available title/metadata do not verify variant-specific case-control evidence. Therefore PS4 cannot be assessed from the available evidence.
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. ... Note 1: Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0.
The evidence identifies other EZH2 substitutions at the same Tyr641/Y646 residue, including Y641F, Y641S, and Y641H in PMID:21078963, and recurrent Y641 mutations in PMID:20081860 and PMID:21190999. However, the available records do not establish one of those alternate missense variants as a pathogenic variant under generic ACMG/AMP criteria; they are primarily somatic lymphoma and functional studies, and the ClinVar record for the queried variant is not an expert-reviewed germline classification. The same-residue comparator evidence therefore cannot be safely converted to PM5.
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
PM6 cannot be assessed because no patient-level germline de novo observation is documented, and there is no evidence that the variant was assumed de novo without confirmation of paternity and maternity. The available literature concerns somatic EZH2 mutations in lymphoma and does not establish PM6.
Assumed de novo, but without confirmation of paternity and maternity.
PP1 cannot be assessed because no affected family members carrying the variant, informative meioses, or co-segregation results are documented. Although germline EZH2-related disease is mentioned in the case context, the available variant-specific literature is somatic oncology literature and supplies no family segregation data.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease.
The available case evidence describes EZH2 missense disease biology and recurrent somatic missense changes, but it does not provide the gene-level benign missense rate or a governing threshold demonstrating a low rate of benign missense variation. It also does not establish the required generic ACMG/AMP gene-level combination as a validated germline disease mechanism for this criterion. PP2 is therefore not assessed.
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
The governing PP4 rule requires a patient's phenotype or family history that is highly specific for a disease with a single genetic etiology. The case evidence identifies EZH2 p.Tyr646Asn and oncology-related literature, but does not provide the patient's phenotype, family history, or a sufficiently specific single-etiology clinical presentation. The criterion therefore cannot be assessed.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
BS2 is not assessed. The supplied evidence contains population-database absence and a somatic ClinVar record, but no observation of this variant in a healthy adult individual, no zygosity, and no information establishing that an observed individual was unaffected at an age appropriate for a fully penetrant early-onset disorder. Population absence cannot establish BS2.
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
BS4 cannot be assessed because the available evidence does not identify affected family members who were tested for the variant and found not to carry it. No family structure, phenotype adjudication, or non-segregation results are documented, so lack of segregation cannot be distinguished from absence of family data.
Lack of segregation in affected members of a family.
BP2 cannot be assessed because the available evidence does not document a pathogenic variant in trans or cis with NM_004456.5:c.1936T>A, does not provide parental or offspring phase testing, and does not report affected-proband allelic observations usable for this criterion. Somatic reports of EZH2 Y641N with a wild-type allele do not establish the required pathogenic-variant phase relationship.
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
The governing BP5 rule requires the variant to be found in a case with an alternate molecular basis for disease. The available case evidence and reviewed papers do not document an individual case carrying EZH2 p.Tyr646Asn together with an independently established alternate molecular cause of that disease. BP5 cannot be assessed.
Variant found in a case with an alternate molecular basis for disease.
PVS1 (ClinGen SVI PVS1 recommendations, PMC6185798, pvs1_generic_framework) applies only to null variant classes — nonsense, frameshift, canonical ±1/2 splice-consensus, translation-initiation-codon loss, and stop-loss variants — each expected to trigger nonsense-mediated decay or otherwise abolish normal protein function. NM_004456.5:c.1936T>A in EZH2 is a missense substitution predicted to produce NP_004447.2:p.(Tyr646Asn). As a result, no null-variant mechanism (nonsense-mediated decay, truncation, or canonical splice disruption) is triggered by this variant class, so PVS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PVS1 for EZH2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_null_variant_class
PM3 is not applicable because its governing definition is restricted to recessive disorders. The available EZH2 disease context is a dominant-negative Weaver syndrome context, and no recessive inheritance context is established for this variant.
For recessive disorders, detected in trans with a pathogenic variant...This requires testing of parents (or offspring) to determine phase.
PM4 (Richards et al. 2015, PMID:25741868) applies to protein length changes: in-frame insertions/deletions in a non-repetitive region, or stop-loss variants that extend the protein past the reference stop codon. NM_004456.5:c.1936T>A in EZH2 is a missense substitution predicted to produce NP_004447.2:p.(Tyr646Asn). As a result, no change in protein length occurs, so there is nothing for this criterion to evaluate, so PM4's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM4 for EZH2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_stop_loss_or_nonrepeat_indel
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_004456.5:c.1936T>A in EZH2 is a missense substitution predicted to produce NP_004447.2:p.(Tyr646Asn). As a result, the variant does not alter protein length within a repeat region, so there is nothing for this criterion to evaluate, so BP3's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP3 for EZH2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_repeat_region_indel
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_004456.5:c.1936T>A in EZH2 is a missense substitution predicted to produce NP_004447.2:p.(Tyr646Asn). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for EZH2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
Every interpreted variant in EZH2, mapped onto the exon structure of NM_004456.5. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
Absent from gnomAD v4.1.
Absent from gnomAD v2.1.
Not available in gnomAD-Canada v1.0.
NM_004456.5:c.1936T>A is a missense variant, NP_004447.2:p.(Tyr646Asn), so the applicable generic computational path is REVEL only. The REVEL score is 0.895, meeting the supplied PP3 moderate threshold of >= 0.773 from the ClinGen SVI REVEL calibration (Pejaver et al. 2022, PMID:36413997). SpliceAI is not used for PP3 because splice prediction is not the governing path for this missense variant; BayesDel is not available for generic PP3/BP4 strength assignment because no generic ACMG-strength calibration is established.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.). ... Missense variant -> REVEL only. Its SpliceAI score says nothing about whether the amino-acid substitution is tolerated, so 'no predicted splice impact' is never BP4 support for a missense variant. ... PP3 (moderate): >= 0.773 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
NM_004456.5:c.1936T>A is a missense variant, so BP4 must be judged by REVEL only. REVEL is 0.895, which does not meet the supplied BP4 supporting threshold of <= 0.29 from the ClinGen SVI REVEL calibration (Pejaver et al. 2022, PMID:36413997). The SpliceAI max delta of 0.006 cannot substitute for the missense REVEL path, and the BayesDel score is not usable because no generic ACMG-strength calibration is established.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc). ... Missense variant -> REVEL only. Its SpliceAI score says nothing about whether the amino-acid substitution is tolerated, so 'no predicted splice impact' is never BP4 support for a missense variant. ... BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_004456.5:c.1936T>A in EZH2 is a missense substitution predicted to produce NP_004447.2:p.(Tyr646Asn). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for EZH2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.895. BayesDel score = 0.50006.
8 paper records listed. 3 cited in the classification.
Recently, somatic mutations of Tyr641 (Y641F, Y641N, Y641S, and Y641H) of EZH2 were reported to be associated with follicular lymphoma (FL) and the germinal-center B-cell like (GCB) subtype of diffuse large B-cell lymphoma (DLBCL) (1).
Location Results and Discussion; Table 1; Fig. 3
Context In vitro methyltransferase assays using recombinant PRC2 complexes containing wild-type or mutant EZH2, with H3K27 peptides and avian nucleosomes; kinetic modeling and analysis of heterozygous EZH2 Y641N lymphoma cell lines.
Strikingly, EZH2Y641 mutants showed (Figure 4) strongly reduced activity on unmethylated or monomethylated peptides but markedly enhanced activity on dimethylated peptides compared with EZH2 wild-type containing PRC2 complexes.
Location Introduction; Results sections on EZH2Y641 lymphoma cell lines and Y641-containing PRC2 complexes; Table 1
Context Heterozygous EZH2-mutant lymphoma cell lines and primary DLBCL tumor samples; expression studies and in vitro 3H-SAM methyltransferase assays using recombinant PRC2 complexes and H3K27 peptides.
These data demonstrate that Y641 mutation reinforces the GC phenotype-driving function of wild-type EZH2, resulting in an expansion of these proliferative and mutagenic cells.
Location Results, “Mutant EZH2 Induces Germinal Center Hyperplasia,” Figure 2 and accompanying text
Context Conditional mouse model expressing Ezh2Y641N in germinal-center B cells; immunization, flow cytometry, splenic immunohistochemistry, H3K27me3 immunoblotting, and EZH2 inhibitor treatment.
The results (Figure 2) indicated that, compared to wild-type EZH2, all four Y641 mutants consistently demonstrated a marked reduction (~7-fold) in their ability to tri-methylate the H3K27 peptide.
Results, paragraph describing the in vitro EZH2 H3K27 tri-methylation assay; concluding paragraph
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
Absent from gnomAD v4.1.
Absent from gnomAD v2.1.
Not available in gnomAD-Canada v1.0.
This variant has been reported in ClinVar but submission details could not be extracted. (ClinVarID = 376217)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.895. BayesDel score = 0.50006.
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Gain-of-function; curated oncogenicity label: Likely Oncogenic.
This variant lies in a statistically significant hotspot.
This variant lies in a statistically significant hotspot.