ARID2AT-rich interaction domain 2
Autism Reports / Total Reports
5 / 12Rare Variants / Common Variants
33 / 0Aliases
ARID2, BAF200, CSS6, p200Associated Syndromes
Coffin-Siris syndrome 6, Coffin-Siris syndrome 6, DD, IDChromosome Band
12q12Associated Disorders
DD/NDD, ADHD, IDRelevance to Autism
A de novo missense variant that was predicted to be damaging was observed in the ARID2 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, while a de novo splice-site variant in this gene was identified in an ASD proband from the ASPIRE cohort in Callaghan et al., 2019. Heterozygous variants in the ARID2 gene are also associated with a form of Coffin-Siris syndrome (Coffin-Siris syndrome 6; OMIM 617808); in addition to intellectual disability and dysmorphic features, individuals with this syndrome frequently present with behavioral abnormalities such as ADHD, tics, and autistic behavior such as routine-driven and/or rigid behavior and hand-flapping (Shang et al., 2015; Branswig et al., 2017; Van Paemel et al., 2017; Gazdagh et al., 2019).
Molecular Function
This gene encodes a member of the AT-rich interactive domain (ARID)-containing family of DNA-binding proteins. Members of the ARID family have roles in embryonic patterning, cell lineage gene regulation, cell cycle control, transcriptional regulation and chromatin structure modification. This protein functions as a subunit of the polybromo- and BRG1-associated factor or PBAF (SWI/SNF-B) chromatin remodeling complex which facilitates ligand-dependent transcriptional activation by nuclear receptors.
External Links
SFARI Genomic Platforms
Reports related to ARID2 (12 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 | Mutations in ARID2 are associated with intellectual disabilities | Shang L , et al. (2015) | No | DD, ID, ADHD |
3 | Support | Heterozygosity for ARID2 loss-of-function mutations in individuals with a Coffin-Siris syndrome-like phenotype | Bramswig NC , et al. (2017) | No | - |
4 | Support | Prevalence and architecture of de novo mutations in developmental disorders | et al. (2017) | No | - |
5 | Support | Confirmation of an ARID2 defect in SWI/SNF-related intellectual disability | Van Paemel R , et al. (2017) | No | - |
6 | Support | Extending the clinical and genetic spectrum of ARID2 related intellectual disability. A case series of 7 patients | Gazdagh G , et al. (2018) | No | - |
7 | Recent Recommendation | Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort | Callaghan DB , et al. (2019) | Yes | - |
8 | Support | A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders | Suzuki T et al. (2020) | No | - |
9 | Support | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | - |
10 | Support | - | Lee Y et al. (2021) | No | - |
11 | Support | - | Hu C et al. (2022) | Yes | - |
12 | Support | - | Zhou X et al. (2022) | Yes | - |
Rare Variants (33)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_loss | - | - | - | 28884947 | Van Paemel R , et al. (2017) | |
- | - | copy_number_loss | De novo | NA | - | 34706719 | Lee Y et al. (2021) | |
- | - | copy_number_loss | Unknown | - | - | 29698805 | Gazdagh G , et al. (2018) | |
c.4444C>T | p.Gln1482Ter | stop_gained | De novo | NA | - | 28135719 | et al. (2017) | |
c.2983C>T | p.Gln995Ter | stop_gained | De novo | NA | - | 35741772 | Hu C et al. (2022) | |
c.2377C>T | p.Gln793Ter | stop_gained | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.1028T>A | p.Leu343Ter | stop_gained | Unknown | - | - | 26238514 | Shang L , et al. (2015) | |
c.940C>T | p.Arg314Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1652C>T | p.Ser551Leu | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.2T>G | p.Met1? | initiator_codon_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.4318C>T | p.Gln1440Ter | stop_gained | De novo | NA | - | 26238514 | Shang L , et al. (2015) | |
c.399C>G | p.Tyr133Ter | stop_gained | De novo | NA | - | 29698805 | Gazdagh G , et al. (2018) | |
c.5141C>T | p.Ser1714Phe | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.4444C>T | p.Gln1482Ter | stop_gained | De novo | NA | - | 29698805 | Gazdagh G , et al. (2018) | |
c.5036G>A | p.Arg1679Gln | missense_variant | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.1330+1G>A | - | splice_site_variant | De novo | NA | - | 31038196 | Callaghan DB , et al. (2019) | |
c.327T>G | p.Asp109Glu | initiator_codon_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.625G>A | p.Val209Met | missense_variant | De novo | NA | Simplex | 35982159 | Zhou X et al. (2022) | |
c.1158dup | p.Asn387Ter | frameshift_variant | De novo | NA | - | 29698805 | Gazdagh G , et al. (2018) | |
c.2122C>T | p.Pro708Ser | missense_variant | Unknown | - | Unknown | 32530565 | Suzuki T et al. (2020) | |
c.4390C>T | p.Arg1464Cys | missense_variant | Familial | Paternal | - | 33004838 | Wang T et al. (2020) | |
c.4687_4690dup | p.Thr1564LysfsTer5 | frameshift_variant | De novo | NA | - | 28135719 | et al. (2017) | |
c.2796A>G | p.Pro932%3D | synonymous_variant | De novo | NA | Simplex | 35982159 | Zhou X et al. (2022) | |
c.940C>T | p.Arg314Cys | missense_variant | De novo | NA | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.2645_2646insCT | p.Val883LeufsTer10 | frameshift_variant | De novo | NA | - | 28135719 | et al. (2017) | |
c.300del | p.Tyr100Ter | frameshift_variant | Unknown | Not maternal | - | 33004838 | Wang T et al. (2020) | |
c.2406del | p.Phe802LeufsTer20 | frameshift_variant | De novo | NA | - | 26238514 | Shang L , et al. (2015) | |
c.26del | p.Pro9LeufsTer49 | frameshift_variant | De novo | NA | - | 28124119 | Bramswig NC , et al. (2017) | |
c.4310del | p.Ala1437GlyfsTer16 | frameshift_variant | De novo | NA | - | 26238514 | Shang L , et al. (2015) | |
c.1932_1936del | p.Gln644HisfsTer61 | frameshift_variant | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.4687_4690dup | p.Thr1564LysfsTer5 | frameshift_variant | De novo | NA | - | 29698805 | Gazdagh G , et al. (2018) | |
c.2645_2646insCT | p.Val883LeufsTer10 | frameshift_variant | De novo | NA | - | 29698805 | Gazdagh G , et al. (2018) | |
c.3280_3281del | p.Ser1094ProfsTer10 | frameshift_variant | De novo | NA | - | 28124119 | Bramswig NC , et al. (2017) |
Common Variants
No common variants reported.
SFARI Gene score
Strong Candidate, Syndromic


A de novo missense variant that was predicted to be damaging was observed in the ARID2 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, while a de novo splice-site variant in this gene was identified in an ASD proband from the ASPIRE cohort in Callaghan et al., 2019. Heterozygous variants in the ARID2 gene are also associated with a form of Coffin-Siris syndrome (Coffin-Siris syndrome 6; OMIM 617808); in addition to intellectual disability and dysmorphic features, individuals with this syndrome frequently present with behavioral abnormalities such as ADHD, tics, and autistic behavior such as routine-driven and/or rigid behavior and hand-flapping (Shang et al., 2015; Branswig et al., 2017; Van Paemel et al., 2017; Gazdagh et al., 2019).
Score Delta: Score remained at 2S
criteria met
See SFARI Gene'scoring criteriaWe 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.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
4/1/2022

Decreased from 3S to 2S
Description
A de novo missense variant that was predicted to be damaging was observed in the ARID2 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, while a de novo splice-site variant in this gene was identified in an ASD proband from the ASPIRE cohort in Callaghan et al., 2019. Heterozygous variants in the ARID2 gene are also associated with a form of Coffin-Siris syndrome (Coffin-Siris syndrome 6; OMIM 617808); in addition to intellectual disability and dysmorphic features, individuals with this syndrome frequently present with behavioral abnormalities such as ADHD, tics, and autistic behavior such as routine-driven and/or rigid behavior and hand-flapping (Shang et al., 2015; Branswig et al., 2017; Van Paemel et al., 2017; Gazdagh et al., 2019).
10/1/2020

Decreased from 3S to 3S
Description
A de novo missense variant that was predicted to be damaging was observed in the ARID2 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, while a de novo splice-site variant in this gene was identified in an ASD proband from the ASPIRE cohort in Callaghan et al., 2019. Heterozygous variants in the ARID2 gene are also associated with a form of Coffin-Siris syndrome (Coffin-Siris syndrome 6; OMIM 617808); in addition to intellectual disability and dysmorphic features, individuals with this syndrome frequently present with behavioral abnormalities such as ADHD, tics, and autistic behavior such as routine-driven and/or rigid behavior and hand-flapping (Shang et al., 2015; Branswig et al., 2017; Van Paemel et al., 2017; Gazdagh et al., 2019).
7/1/2020

Decreased from 3S to 3S
Description
A de novo missense variant that was predicted to be damaging was observed in the ARID2 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, while a de novo splice-site variant in this gene was identified in an ASD proband from the ASPIRE cohort in Callaghan et al., 2019. Heterozygous variants in the ARID2 gene are also associated with a form of Coffin-Siris syndrome (Coffin-Siris syndrome 6; OMIM 617808); in addition to intellectual disability and dysmorphic features, individuals with this syndrome frequently present with behavioral abnormalities such as ADHD, tics, and autistic behavior such as routine-driven and/or rigid behavior and hand-flapping (Shang et al., 2015; Branswig et al., 2017; Van Paemel et al., 2017; Gazdagh et al., 2019).
10/1/2019

Decreased from 4S to 3S
New Scoring Scheme
Description
A de novo missense variant that was predicted to be damaging was observed in the ARID2 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, while a de novo splice-site variant in this gene was identified in an ASD proband from the ASPIRE cohort in Callaghan et al., 2019. Heterozygous variants in the ARID2 gene are also associated with a form of Coffin-Siris syndrome (Coffin-Siris syndrome 6; OMIM 617808); in addition to intellectual disability and dysmorphic features, individuals with this syndrome frequently present with behavioral abnormalities such as ADHD, tics, and autistic behavior such as routine-driven and/or rigid behavior and hand-flapping (Shang et al., 2015; Branswig et al., 2017; Van Paemel et al., 2017; Gazdagh et al., 2019).
Reports Added
[New Scoring Scheme]7/1/2019

Increased from to 4S
Description
A de novo missense variant that was predicted to be damaging was observed in the ARID2 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, while a de novo splice-site variant in this gene was identified in an ASD proband from the ASPIRE cohort in Callaghan et al., 2019. Heterozygous variants in the ARID2 gene are also associated with a form of Coffin-Siris syndrome (Coffin-Siris syndrome 6; OMIM 617808); in addition to intellectual disability and dysmorphic features, individuals with this syndrome frequently present with behavioral abnormalities such as ADHD, tics, and autistic behavior such as routine-driven and/or rigid behavior and hand-flapping (Shang et al., 2015; Branswig et al., 2017; Van Paemel et al., 2017; Gazdagh et al., 2019).
Krishnan Probability Score
Score 0.57157283085621
Ranking 770/25841 scored genes
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ExAC Score
Score 0.9999990531281
Ranking 297/18225 scored genes
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Iossifov Probability Score
Score 0.866
Ranking 179/239 scored genes
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Sanders TADA Score
Score 0.87027442745232
Ranking 4316/18665 scored genes
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Zhang D Score
Score 0.52724919724932
Ranking 342/20870 scored genes
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