BAZ2B

protein-coding

bromodomain adjacent to zinc finger domain 2B, the group of Methyl-CpG binding domain containing|PHD finger proteins|Bromodomain containing

Gene summary

This gene belongs to the bromodomain gene family. Members of this gene family encode proteins that are integral components of chromatin remodeling complexes. The encoded protein showed strong preference for the activating H3K14Ac mark in a histone peptide screen, suggesting a potential role in transcriptional activation. This gene may be associated with susceptibility to sudden cardiac death (SCD). [provided by RefSeq, Aug 2016]

MANE transcript

NM_013450.4

Inheritance

ClinVar variants

P:19U:417B:100

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr2:159,315,312-159,616,569

External References & Databases

Ensembl (ENSG00000123636)

Transcript & Mutation Effects

hg38 • Region Span ~301.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: ClinGen

The *BAZ2B* gene is a member of the BAZ gene family that encodes integral components of chromatin remodeling complexes that modulate transcription, DNA replication, and DNA repair. *BAZ2B* was first reported in relation to autosomal dominant complex neurodevelopmental disorder in 2020 (Scott et al., PMID:31999386). Clinical features in reported probands include neurodevelopmental disorders such as intellectual disability, developmental delay, and autism spectrum disorder. Other features are highly variable, reported only in one or few individuals. At least 24 unique variants (7 nonsense, 3 frameshift, 12 missense, 2 large deletions) have been reported in the literature (PMIDs: 25363768, 28135719, 28554332, 28867142, 31398340, 31981491, 31999386, 33057194). In 26 unrelated probands reported, 19 (73%) variants were *de novo*, 1 inherited from an unaffected parent, and the rest of unknown inheritance. While *BAZ2B* is intolerant to truncating variants (pLI 0.98, gnomAD v2.1.1), it is not significantly constrained for missense variants (Z = 1.33). Thus, in the absence of functional evidence of pathogenicity, missense variants were not scored. Probands with other potential genetic explanations for their neurodevelopmental phenotypes, deletions of *BAZ2B* that encompass additional genes, mosaic variants at low allele frequencies, and truncating variants reported in gnomAD or inherited from reportedly unaffected parents were also not scored since the impact of *BAZ2B* on the phenotype is unclear. Six truncating *de novo* variants in 6 probands from 5 publications (PMIDs: 25363768, 28554332, 31981491, 31999386, 33057194) are included in this curation. Although the total points contained within this curation meet the threshold for a “Moderate” classification, the expert panel elected to downgrade the overall classification to “Limited” while we await additional human genetic evidence. In summary, there is limited evidence at this time to support the relationship between *BAZ2B* and autosomal dominant complex neurodevelopmental disorder. Additional studies are required to verify this gene-disease relationship. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on October 19, 2022 (SOP Version 9).

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BAZ2B variants in ClinVar

11 Conditions Cataloged

Inborn genetic diseasesTotal: 288

not providedTotal: 209

BAZ2B-related disorderTotal: 74

Neurodevelopmental disorderTotal: 10

not specifiedTotal: 8

BAZ2B-related Neurodevelopmental disorderTotal: 5

BAZ2B-associated neurodevelopmental disorderTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013450.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	27 clinvar	4 clinvar	33
missense	2 clinvar	2 clinvar	392 clinvar	65 clinvar	3 clinvar	464
nonsense	2 clinvar	2 clinvar	8 clinvar	1 clinvar		13
start loss		1 clinvar				1
frameshift	3 clinvar	3 clinvar	7 clinvar			13
splice donor/acceptor (+/-2bp)		4 clinvar	8 clinvar			12
Total	7	12	417	93	7	536

Highest pathogenic variant AF is 0.000006580333

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 74 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013450.4	RefSeq	NP_038478.2	35	MANE Select
ENST00000392783.7	Ensembl	ENSP00000376534.2	35	MANE Select
NM_001289975.1	RefSeq	NP_001276904.1	34	Standard
NM_001329857.2	RefSeq	NP_001316786.1	35	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

chromatin remodeling
regulation of transcription by RNA polymerase II

Molecular Function

DNA binding
protein binding
metal ion binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392783
Coding exons: 35
Length: 297714
Individuals with no LoFs: 124982
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125026
p: 0.000176

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.33	971	1.10e+3	0.887	0.0000550	14209
Missense (PolyPhen)		236	338.46	0.69728		4349
Synonymous	0.346	371	380	0.977	0.0000188	4061
Loss of Function	7.73	22	109	0.201	0.00000604	1381

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00039	0.00026	rare
Latino/Admixed American	0.000087	0.000058	rare
Ashkenazi Jewish	0.00070	0.00040	rare
East Asian	0.00017	0.00016	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.000099	0.000098	rare
Other	0.00069	0.00066	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in transcriptional regulation interacting with ISWI.;

Recessive Scores

pRec: 0.0949

Intolerance Scores

LoFtool: 0.244
RVIS EVS: -1.42
RVIS percentile EVS: 4.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.830

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	High	High