Human Gene Module / Chromosome 17 / DNAH17

DNAH17dynein axonemal heavy chain 17

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
9 / 9
Rare Variants / Common Variants
20 / 0
Aliases
DNAH17, DNAHL1,  DNEL2
Associated Syndromes
-
Chromosome Band
17q25.3
Associated Disorders
-
Relevance to Autism

A de novo nonsense variant in the DNAH17 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; this variant was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 40/84,448 expected; hypergeometric P-value of 0.030). Additional missense variants in DNAH17 that are predicted to be damaging have been identifed in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2014), although these variants are also present in external databases such as dbSNP.

Molecular Function

Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. DNAH17 is a heavy chain associated with axonemal dynein.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DNAH17 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
2 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
3 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
4 Recent Recommendation Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
5 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
6 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
7 Support - Alonso-Gonzalez A et al. (2021) Yes -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (20)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.12589-17C>T - intron_variant De novo - - 35982159 Zhou X et al. (2022)
c.9653+7C>T - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.3446C>T p.Thr1149Ile missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.6476C>G p.Pro2159Arg missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.7636G>T p.Asp2546Tyr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2799C>T p.Asn933%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.3799A>T p.Lys1267Ter stop_gained De novo - - 25363760 De Rubeis S , et al. (2014)
c.7737C>T p.Ile2579%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.12279C>T p.His4093%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.6858G>A p.Ser2286= synonymous_variant De novo - - 31452935 Feliciano P et al. (2019)
c.7979C>T p.Ser2660Phe missense_variant De novo - Simplex 28714951 Lim ET , et al. (2017)
c.10045G>A p.Gly3349Arg missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.13202C>T p.Pro4401Leu missense_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.13294C>T p.Arg4432Cys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3114+1G>T - splice_site_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.7752+2T>A - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.3274G>A p.Val1092Ile missense_variant De novo - Simplex 33431980 Alonso-Gonzalez A et al. (2021)
c.1869T>A p.Tyr623Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.11163del p.Leu3722SerfsTer20 frameshift_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.5598del p.Met1867TrpfsTer45 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo nonsense variant in the DNAH17 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; this variant was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 40/84,448 expected; hypergeometric P-value of 0.030). Additional missense variants in DNAH17 that are predicted to be damaging have been identifed in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2014), although these variants are also present in external databases such as dbSNP.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A de novo nonsense variant in the DNAH17 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; this variant was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 40/84,448 expected; hypergeometric P-value of 0.030). Additional missense variants in DNAH17 that are predicted to be damaging have been identifed in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2014), although these variants are also present in external databases such as dbSNP.

1/1/2021
3
icon
3

Decreased from 3 to 3

Description

A de novo nonsense variant in the DNAH17 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; this variant was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 40/84,448 expected; hypergeometric P-value of 0.030). Additional missense variants in DNAH17 that are predicted to be damaging have been identifed in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2014), although these variants are also present in external databases such as dbSNP.

Reports Added
[Exploring the biological role of postzygotic and germinal de novo mutations in ASD2021]
7/1/2020
3
icon
3

Decreased from 3 to 3

Description

A de novo nonsense variant in the DNAH17 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; this variant was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 40/84,448 expected; hypergeometric P-value of 0.030). Additional missense variants in DNAH17 that are predicted to be damaging have been identifed in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2014), although these variants are also present in external databases such as dbSNP.

Reports Added
[Clustering by phenotype and genome-wide association study in autism2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo nonsense variant in the DNAH17 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; this variant was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 40/84,448 expected; hypergeometric P-value of 0.030). Additional missense variants in DNAH17 that are predicted to be damaging have been identifed in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2014), although these variants are also present in external databases such as dbSNP.

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A de novo nonsense variant in the DNAH17 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; this variant was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 40/84,448 expected; hypergeometric P-value of 0.030). Additional missense variants in DNAH17 that are predicted to be damaging have been identifed in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2014), although these variants are also present in external databases such as dbSNP.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2017
icon
4

Increased from to 4

Description

A de novo nonsense variant in the DNAH17 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; this variant was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 40/84,448 expected; hypergeometric P-value of 0.030). Additional missense variants in DNAH17 that are predicted to be damaging have been identifed in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2014), although these variants are also present in external databases such as dbSNP.

Krishnan Probability Score

Score 0.49679428677125

Ranking 2514/25841 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.
Original Source
Sanders TADA Score

Score 0.83344057160657

Ranking 2943/18665 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).
Original Source
Zhang D Score

Score 0.027700330718849

Ranking 7853/20870 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.
Original Source
Submit New Gene

Report an Error