PHF2
  • 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
PHF2 (HGNC:8920) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
PHD finger protein 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
KIAA0662, JHDM1E, CENP-35, KDM7C
%HI
54.82(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.33(Read more about gnomAD LOEUF score)
Cytoband
9q22.31
Genomic Coordinates
GRCh37/hg19: chr9:96338866-96441869 NCBI Ensembl UCSC
GRCh38/hg38: chr9:93576584-93679587 NCBI Ensembl UCSC
MANE Select Transcript
NM_005392.4 ENST00000359246.9 (Read more about MANE Select)
Function
Lysine demethylase that demethylates both histones and non- histone proteins (PubMed:20129925, PubMed:21167174, PubMed:21532585). Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B (PubMed:21532585). Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcri... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-9204
ClinGen Curation ID:
CCID:007654
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
02/27/2019

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Evidence:
  • PUBMED: 25363768
    Iossifov et al (Nature 2014) performed a large whole exome sequencing study of over 2000 families from the Simons Simplex Collection. Found 1 family member with ASD, with a nonsense de novo change in PHF2 (supplemental table 2). The nonsense mutation is in exon 20/22 on the HGMD transcript and is predicted to result in non-sense mediated decay.
  • PUBMED: 27824329
    A 2016 study in Nature Communications sequenced the coding regions of 189 autism risk genes across 1,543 probands from the Autism Clinical and Genetic Resources in China using single-molecule molecular inversion probes. This study reported a patient with ASD and a splice site variant in the acceptor region (not maternally inherited, paternal status unknown).
HI Evidence Comments:
1) Of note in PMID 25363768, found a frameshift mutation is in the last exon 22/22 of the HGMD transcript resulting in a stop gain but may not undergo NMD. Please also note that PMID 22542183 are the same authors describing the same frame mutation/patient mentioned in their 2014 study and then the same frameshift/patient is again described in a 2017 article -- PMID: 28191890 supp Table 1 as the original Iossifov et al study). 2) Also of note in PMID 2782439, there were an additional 2 patients, reported as ASD with no other phenotype info provided, in supplemental data (Table 4). Both were missense variants (both variants also reported in gnomAD, one of these variants was maternally inherited with no phenotype info provided on mom and inheritance was not determined for the second variant as parents’ DNA not available). Counting likely gene disrupting events, to date 2 families (PMID: 25363768) have been reported with de novo changes in PHF2. And in one of the 2 ASD families, the reported frameshift change is not predicted to lead to NMD due to its location in the last exon and therefore not counted (so based on individual case evidence for de novo occurrences and given lack of details/non-specific ASD phenotype, 0.15 points given for the 1 family with the nonsense change from category C ). With respect to the study (PMID: 27824329), the authors did not put PHF2 high on the list of autism risk genes and inheritance was unknown in 2 of the 3 cases reported (no points given in 'unknown inheritance' category since ASD phenotype for this gene is relatively non-specific) In terms of HI predictors, , PHF2 has a pLI score of 1 with a low observed/expected ratio of 0.08 (52 expected and 4 observed as of Feb 2019). But %HI is 54.82 from DECIPHER. The weight of these two predictive scores are not necessarily in agreement with each other -- no points given for these predictors.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Focal duplications of PHF2 not reported

Genomic View

Select assembly: (NC_000009.11) (NC_000009.12)