rs41277434

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004456.5(EZH2):c.2110+6T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 1,600,172 control chromosomes in the GnomAD database, including 3,257 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 290 hom., cov: 33)

Exomes 𝑓: 0.058 ( 2967 hom. )

Consequence

EZH2
NM_004456.5 splice_region, intron

Scores

Splicing: ADA: 0.0003168

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.791

Variant links:

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]

EZH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-148809304-A-C is Benign according to our data. Variant chr7-148809304-A-C is described in ClinVar as [Benign]. Clinvar id is 137273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EZH2	NM_004456.5 link	c.2110+6T>G		splice_region_variant, intron_variant	Intron 18 of 19	ENST00000320356.7	NP_004447.2	Q15910-2A0A090N8E9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EZH2	ENST00000320356.7 link	c.2110+6T>G		splice_region_variant, intron_variant	Intron 18 of 19	1	NM_004456.5	ENSP00000320147.2		Q15910-2

Frequencies

GnomAD3 genomes

AF:

0.0503

AC:

7661

AN:

152232

Hom.:

286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0192

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.0571

Gnomad EAS

AF:

0.0373

Gnomad SAS

AF:

0.0457

Gnomad FIN

AF:

0.0662

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0547

Gnomad OTH

AF:

0.0545

GnomAD3 exomes

AF:

0.0682

AC:

17153

AN:

251348

Hom.:

952

AF XY:

0.0651

AC XY:

8850

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.0587

Gnomad EAS exome

AF:

0.0360

Gnomad SAS exome

AF:

0.0468

Gnomad FIN exome

AF:

0.0690

Gnomad NFE exome

AF:

0.0526

Gnomad OTH exome

AF:

0.0692

GnomAD4 exome

AF:

0.0576

AC:

83363

AN:

1447822

Hom.:

2967

Cov.:

AF XY:

0.0571

AC XY:

40944

AN XY:

716946

show subpopulations

Gnomad4 AFR exome

AF:

0.0174

Gnomad4 AMR exome

AF:

0.173

Gnomad4 ASJ exome

AF:

0.0599

Gnomad4 EAS exome

AF:

0.0526

Gnomad4 SAS exome

AF:

0.0459

Gnomad4 FIN exome

AF:

0.0665

Gnomad4 NFE exome

AF:

0.0546

Gnomad4 OTH exome

AF:

0.0573

GnomAD4 genome

AF:

0.0503

AC:

7663

AN:

152350

Hom.:

290

Cov.:

AF XY:

0.0511

AC XY:

3805

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0191

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0571

Gnomad4 EAS

AF:

0.0370

Gnomad4 SAS

AF:

0.0456

Gnomad4 FIN

AF:

0.0662

Gnomad4 NFE

AF:

0.0547

Gnomad4 OTH

AF:

0.0539

Alfa

AF:

0.0555

Hom.:

199

Bravo

AF:

0.0552

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

EpiCase

AF:

0.0579

EpiControl

AF:

0.0561

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 19, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 07, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Weaver syndrome

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00032

dbscSNV1_RF

Benign

0.040

SpliceAI score (max)

0.12

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