Human Gene Module / Chromosome 9 / PHF2

PHF2PHD finger protein 2

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 5
Rare Variants / Common Variants
7 / 0
Aliases
PHF2, CENP-35,  GRC5,  JHDM1E
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
9q22.31
Associated Disorders
-
Relevance to Autism

Two de novo loss-of-function variants in the PHF2 gene have been identified in ASD probands from the Simons Simplex Collection (refs).

Molecular Function

Lysine demethylase that demethylates both histones and non-histone proteins. PHD finger genes are thought to belong to a diverse group of transcriptional regulators possibly affecting eukaryotic gene expression by influencing chromatin structure.

Reports related to PHF2 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo gene disruptions in children on the autistic spectrum. Iossifov I , et al. (2012) Yes -
2 Recent Recommendation The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
3 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
4 Support De novo genic mutations among a Chinese autism spectrum disorder cohort. Wang T , et al. (2016) Yes -
5 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.860C>T p.Ala287Val missense_variant Unknown - - 27824329 Wang T , et al. (2016)
c.3203-2A>G - splice_site_variant Unknown Not maternal - 27824329 Wang T , et al. (2016)
c.860C>T p.Ala287Val missense_variant Familial Maternal - 27824329 Wang T , et al. (2016)
c.2749C>T p.Gln917Ter stop_gained De novo NA Simplex 25363768 Iossifov I , et al. (2014)
c.3264del p.His1089IlefsTer71 frameshift_variant De novo NA Simplex 22542183 Iossifov I , et al. (2012)
c.2963_2964insT p.Ala989GlyfsTer27 frameshift_variant Familial - Simplex 28263302 C Yuen RK , et al. (2017)
c.2964_2965insCCTCCACCACACCA p.Ala989ProfsTer103 frameshift_variant Familial - Simplex 28263302 C Yuen RK , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo LoF variants in the PHF2 gene (one frameshift, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768).

Score Delta: Decreased from 3 to 2

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Two de novo LoF variants in the PHF2 gene (one frameshift, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768).

Reports Added
[New Scoring Scheme]
10/1/2016
3
icon
3

Decreased from 3 to 3

Description

Two de novo LoF variants in the PHF2 gene (one frameshift, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768).

1/1/2016
3
icon
3

Decreased from 3 to 3

Description

Two de novo LoF variants in the PHF2 gene (one frameshift, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768).

10/1/2014
icon
3

Increased from to 3

Description

Two de novo LoF variants in the PHF2 gene (one frameshift, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768).

Krishnan Probability Score

Score 0.53899630987803

Ranking 1451/25841 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 0.99413213716592

Ranking 1598/18225 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
Iossifov Probability Score

Score 0.971

Ranking 54/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Sanders TADA Score

Score 0.031890865313833

Ranking 39/18665 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).
Larsen Cumulative Evidence Score

Score 18

Ranking 114/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.32277128352156

Ranking 2398/20870 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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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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