7-148807624-AG-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004456.5(EZH2):c.*21del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (44114 hom., cov: 0)
  • Exomes 𝑓: 0.69 (339386 hom.)
• Consequence: EZH2 NM_004456.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0530

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 7-148807624-AG-A is Benign according to our data. Variant chr7-148807624-AG-A is described in ClinVar as [Benign]. Clinvar id is 259400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-148807624-AG-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EZH2	NM_004456.5	c.*21del		3_prime_UTR_variant	20/20	ENST00000320356.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EZH2	ENST00000320356.7	c.*21del		3_prime_UTR_variant	20/20	1	NM_004456.5	P4

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114217 AN: 151728 Hom.: 44056 Cov.: 0

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.736

GnomAD3 exomes AF: 0.685 AC: 140510 AN: 205250 Hom.: 48709 AF XY: 0.677 AC XY: 74040 AN XY: 109382

Gnomad AFR exome AF: 0.934

Gnomad AMR exome AF: 0.721

Gnomad ASJ exome AF: 0.678

Gnomad EAS exome AF: 0.648

Gnomad SAS exome AF: 0.663

Gnomad FIN exome AF: 0.595

Gnomad NFE exome AF: 0.670

Gnomad OTH exome AF: 0.683

GnomAD4 exome AF: 0.688 AC: 980410 AN: 1425804 Hom.: 339386 Cov.: 0 AF XY: 0.687 AC XY: 485109 AN XY: 706560

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.724

Gnomad4 ASJ exome AF: 0.683

Gnomad4 EAS exome AF: 0.655

Gnomad4 SAS exome AF: 0.676

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.684

Gnomad4 OTH exome AF: 0.696

GnomAD4 genome AF: 0.753 AC: 114337 AN: 151846 Hom.: 44114 Cov.: 0 AF XY: 0.749 AC XY: 55535 AN XY: 74158

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.736

Alfa AF: 0.714 Hom.: 7112

Bravo AF: 0.774

Asia WGS AF: 0.694 AC: 2414 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Weaver syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3217095; hg19: chr7-148504716;