rs2072407

Variant names:

• chr7-148811741-A-G
• rs2072407
• NM_004456.5:c.1852-21T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-148811741-A-G
• chr7-148811741-A-C
• chr7-148811741-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004456.5(EZH2):​c.1852-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,595,956 control chromosomes in the GnomAD database, including 355,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34810 hom., cov: 31)
  • Exomes 𝑓: 0.67 (320846 hom.)
• Consequence: EZH2 NM_004456.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.352
• Publications: 18 publications found

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 Gene-Disease associations (from GenCC):

• Weaver syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-148811741-A-G is Benign according to our data. Variant chr7-148811741-A-G is described in ClinVar as Benign. ClinVar VariationId is 670472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004456.5. 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
	EZH2	NM_004456.5	MANE Select	c.1852-21T>C		intron	N/A	NP_004447.2
	EZH2	NM_001203247.2		c.1837-21T>C		intron	N/A	NP_001190176.1	Q15910-1
	EZH2	NM_001203248.2		c.1810-21T>C		intron	N/A	NP_001190177.1	Q15910-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EZH2	ENST00000320356.7	TSL:1 MANE Select	c.1852-21T>C		intron	N/A	ENSP00000320147.2	Q15910-2
	EZH2	ENST00000460911.5	TSL:1	c.1837-21T>C		intron	N/A	ENSP00000419711.1	Q15910-1
	EZH2	ENST00000350995.6	TSL:1	c.1720-21T>C		intron	N/A	ENSP00000223193.2	Q15910-3

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102472 AN: 151810 Hom.: 34787 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.677

GnomAD2 exomes AF: 0.669 AC: 162544 AN: 243020 AF XY: 0.664

Gnomad AFR exome AF: 0.707

Gnomad AMR exome AF: 0.728

Gnomad ASJ exome AF: 0.679

Gnomad EAS exome AF: 0.668

Gnomad FIN exome AF: 0.590

Gnomad NFE exome AF: 0.671

Gnomad OTH exome AF: 0.663

GnomAD4 exome AF: 0.666 AC: 961145 AN: 1444028 Hom.: 320846 Cov.: 26 AF XY: 0.664 AC XY: 477616 AN XY: 719260

African (AFR) AF: 0.717 AC: 23799 AN: 33214

American (AMR) AF: 0.728 AC: 32383 AN: 44466

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 17752 AN: 26038

East Asian (EAS) AF: 0.660 AC: 26124 AN: 39558

South Asian (SAS) AF: 0.619 AC: 53097 AN: 85838

European-Finnish (FIN) AF: 0.591 AC: 27641 AN: 46732

Middle Eastern (MID) AF: 0.664 AC: 3819 AN: 5748

European-Non Finnish (NFE) AF: 0.668 AC: 736881 AN: 1102524

Other (OTH) AF: 0.662 AC: 39649 AN: 59910

GnomAD4 genome AF: 0.675 AC: 102549 AN: 151928 Hom.: 34810 Cov.: 31 AF XY: 0.671 AC XY: 49866 AN XY: 74270

African (AFR) AF: 0.709 AC: 29345 AN: 41408

American (AMR) AF: 0.725 AC: 11068 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2339 AN: 3466

East Asian (EAS) AF: 0.672 AC: 3469 AN: 5166

South Asian (SAS) AF: 0.614 AC: 2954 AN: 4808

European-Finnish (FIN) AF: 0.564 AC: 5944 AN: 10542

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45258 AN: 67958

Other (OTH) AF: 0.679 AC: 1429 AN: 2106

Alfa AF: 0.668 Hom.: 7360

Bravo AF: 0.692

Asia WGS AF: 0.657 AC: 2286 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Weaver syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.46
DANN	Benign	0.59
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs2072407; hg19: chr7-148508833; COSMIC: COSV57445837;