Human Gene Module / Chromosome 2 / BAZ2B

BAZ2Bbromodomain adjacent to zinc finger domain 2B

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
11 / 0
Aliases
BAZ2B, WALp4
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
2q24.2
Associated Disorders
-
Relevance to Autism

Two de novo variants in the BAZ2B gene (a loss-of-function variant and a damaging missense variant) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. A second loss-of-function (LoF) variant in BAZ2B was identified in a patient presenting with ASD, moderate intellectual disability, and macrocephaly in Bowling et al., 2017. A third LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017. Scott et al., 2020 identified seven individuals with heterozygous deletions, nonsense, or de novo missense variants affecting BAZ2B, all of whom presented with developmental delay, intellectual disability, and/or ASD; most of these individuals also presented with dysmorphic features and/or congenital anomalies.

Molecular Function

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.

Reports related to BAZ2B (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
3 Support Genomic diagnosis for children with intellectual disability and/or developmental delay. Bowling KM , et al. (2017) Yes -
4 Recent Recommendation Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder. Krupp DR , et al. (2017) Yes -
5 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks. Ruzzo EK , et al. (2019) Yes -
6 Recent recommendation BAZ2B haploinsufficiency as a cause of developmental delay, intellectual disability, and autism spectrum disorder. Scott TM , et al. (2020) Yes -
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - Unknown 31999386 Scott TM , et al. (2020)
c.242C>G p.Ser81Ter stop_gained De novo NA - 28554332 Bowling KM , et al. (2017)
c.628C>T p.Arg210Ter stop_gained Unknown - Simplex 31999386 Scott TM , et al. (2020)
c.242C>G p.Ser81Ter stop_gained De novo NA Simplex 31999386 Scott TM , et al. (2020)
c.3868C>T p.Arg1290Ter stop_gained De novo NA Simplex 28867142 Krupp DR , et al. (2017)
c.349C>T p.Arg117Ter stop_gained De novo NA Simplex 27479843 Lelieveld SH et al. (2016)
c.4893A>T p.Ser1631= missense_variant De novo NA Simplex 31999386 Scott TM , et al. (2020)
c.1874A>T p.Asp625Val missense_variant De novo NA Simplex 25363768 Iossifov I et al. (2014)
c.2126G>A p.Cys709Tyr missense_variant De novo NA Multiplex 31999386 Scott TM , et al. (2020)
c.4490C>G p.Ser1497Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.6014dup p.Asn2005LysfsTer5 frameshift_variant De novo NA Simplex 25363768 Iossifov I et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Two de novo variants in the BAZ2B gene (a loss-of-function variant and a damaging missense variant) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. A second loss-of-function (LoF) variant in BAZ2B was identified in a patient presenting with ASD, moderate intellectual disability, and macrocephaly in Bowling et al., 2017. A third LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

Score Delta: Score remained at 2

1

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

1/1/2020
2
icon
2

Score remained at 2

Description

Two de novo variants in the BAZ2B gene (a loss-of-function variant and a damaging missense variant) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. A second loss-of-function (LoF) variant in BAZ2B was identified in a patient presenting with ASD, moderate intellectual disability, and macrocephaly in Bowling et al., 2017. A third LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

10/1/2019
2
icon
1

Decreased from 2 to 1

New Scoring Scheme
Description

Two de novo variants in the BAZ2B gene (a loss-of-function variant and a damaging missense variant) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. A second loss-of-function (LoF) variant in BAZ2B was identified in a patient presenting with ASD, moderate intellectual disability, and macrocephaly in Bowling et al., 2017. A third LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

Reports Added
[New Scoring Scheme]
7/1/2019
2
icon
2

Decreased from 2 to 2

Description

Two de novo variants in the BAZ2B gene (a loss-of-function variant and a damaging missense variant) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. A second loss-of-function (LoF) variant in BAZ2B was identified in a patient presenting with ASD, moderate intellectual disability, and macrocephaly in Bowling et al., 2017. A third LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

10/1/2017
icon
2

Increased from to 2

Description

Two de novo variants in the BAZ2B gene (a loss-of-function variant and a damaging missense variant) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. A second loss-of-function (LoF) variant in BAZ2B was identified in a patient presenting with ASD, moderate intellectual disability, and macrocephaly in Bowling et al., 2017. A third LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

Krishnan Probability Score

Score 0.56693138140938

Ranking 1198/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
ExAC Score

Score 0.9999214403635

Ranking 647/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.23424086129119

Ranking 132/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Zhang D Score

Score 0.33369147297537

Ranking 2236/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
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