PHF2PHD finger protein 2
Autism Reports / Total Reports
8 / 8Rare Variants / Common Variants
9 / 0Chromosome Band
9q22.31Associated Disorders
-Genetic Category
Rare Single Gene MutationRelevance 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.
External Links
SFARI Genomic Platforms
Reports related to PHF2 (8 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 | Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci | Sanders SJ , et al. (2015) | Yes | - |
| 5 | Support | De novo genic mutations among a Chinese autism spectrum disorder cohort | Wang T , et al. (2016) | Yes | - |
| 6 | Support | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
| 7 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 8 | Support | - | Zhou X et al. (2022) | Yes | - |
Rare Variants (9)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.647C>T | p.Ser216Leu | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.860C>T | p.Ala287Val | missense_variant | Unknown | - | - | 27824329 | Wang T , et al. (2016) | |
| c.1148-27C>G | - | intron_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.2749C>T | p.Gln917Ter | stop_gained | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| 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.3264del | p.His1089IlefsTer71 | frameshift_variant | De novo | - | 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
1
High Confidence
Score Delta: Score remained at 1
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.
4/1/2022
2
1
Decreased from 2 to 1
1/1/2020
2
2
Decreased from 2 to 2
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).
10/1/2019
3
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]4/1/2017
3
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).
Reports Added
[De novo gene disruptions in children on the autistic spectrum.2012] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017]10/1/2016
3
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
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
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 Washingtonâs 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.