PPP2R5DProtein phosphatase 2, regulatory subunit B', delta
Autism Reports / Total Reports
8 / 21Rare Variants / Common Variants
51 / 0Chromosome Band
6p21.1Associated Disorders
ID, ASDGenetic Category
Rare Single Gene Mutation, SyndromicRelevance to Autism
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies.
Molecular Function
This gene encodes a delta isoform of the regulatory subunit B56 subfamily and belongs to the phosphatase 2A regulatory subunit B family, which might modulate substrate selectivity and catalytic activity of protein phosphatase 2A, which is one of the four major Ser/Thr phosphatases and has been implicated in the negative control of cell growth and division.
Reports related to PPP2R5D (21 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
2 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | - |
3 | Support | Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth | Loveday C , et al. (2015) | No | - |
4 | Recent Recommendation | B56?-related protein phosphatase 2A dysfunction identified in patients with intellectual disability | Houge G , et al. (2015) | No | - |
5 | Primary | De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism | Shang L , et al. (2015) | No | ASD |
6 | Support | Clinical exome sequencing: results from 2819 samples reflecting 1000 families | Trujillano D , et al. (2016) | No | ID, macrocephaly, hypotonia |
7 | Support | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
8 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay | Bowling KM , et al. (2017) | Yes | Hypotonia, macrocephaly |
9 | Support | Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains | Geisheker MR , et al. (2017) | Yes | - |
10 | Support | Expanding the genetic heterogeneity of intellectual disability | Anazi S , et al. (2017) | No | Macrocephaly |
11 | Support | Variation in a range of mTOR-related genes associates with intracranial volume and intellectual disability | Reijnders MRF , et al. (2017) | No | Macrocephaly |
12 | Support | Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism | Yeung KS , et al. (2018) | No | ASD |
13 | Support | Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder | Takata A , et al. (2018) | Yes | - |
14 | Support | Variant recurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense variants | Lecoquierre F , et al. (2019) | No | - |
15 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
16 | Support | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | - |
17 | Support | - | Brunet T et al. (2021) | No | - |
18 | Support | - | Hiraide T et al. (2021) | No | - |
19 | Support | - | Pode-Shakked B et al. (2021) | No | ASD, epilepsy/seizures |
20 | Support | - | Mahjani B et al. (2021) | Yes | - |
21 | Support | - | ÃÂlvarez-Mora MI et al. (2022) | No | - |
Rare Variants (51)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.*76C>T | - | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.-183C>T | - | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.-200G>A | - | missense_variant | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.92C>T | p.Thr31Met | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.139G>A | p.Glu47Lys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.145G>A | p.Glu49Lys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.202C>T | p.Arg68Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.253G>A | p.Asp85Asn | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.263T>C | p.Phe88Ser | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.655C>T | p.Arg219Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1150C>T | p.Leu384%3D | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1727C>T | p.Pro576Leu | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
AAGAG>AAG | - | frameshift_variant | De novo | - | Simplex | 28263302 | C Yuen RK et al. (2017) | |
c.139G>A | p.Glu47Lys | missense_variant | De novo | NA | - | 26168268 | Houge G , et al. (2015) | |
c.145G>A | p.Glu49Lys | missense_variant | De novo | NA | - | 26168268 | Houge G , et al. (2015) | |
c.157C>T | p.Pro53Ser | missense_variant | De novo | NA | - | 26168268 | Houge G , et al. (2015) | |
c.598G>A | p.Glu200Lys | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
c.592G>A | p.Glu198Lys | missense_variant | De novo | NA | - | 26168268 | Houge G , et al. (2015) | |
c.598G>A | p.Glu200Lys | missense_variant | De novo | NA | - | 26168268 | Houge G , et al. (2015) | |
c.619T>A | p.Trp207Arg | missense_variant | De novo | NA | - | 26168268 | Houge G , et al. (2015) | |
c.589G>A | p.Glu197Lys | missense_variant | De novo | NA | - | 26576547 | Shang L , et al. (2015) | |
c.592G>A | p.Glu198Lys | missense_variant | De novo | NA | - | 26576547 | Shang L , et al. (2015) | |
c.598G>A | p.Glu200Lys | missense_variant | De novo | NA | - | 26576547 | Shang L , et al. (2015) | |
c.805G>A | p.Glu269Lys | missense_variant | De novo | NA | - | 26576547 | Shang L , et al. (2015) | |
c.139G>A | p.Glu47Lys | missense_variant | De novo | NA | - | 29296277 | Yeung KS , et al. (2018) | |
c.1258G>A | p.Glu420Lys | missense_variant | De novo | NA | - | 26576547 | Shang L , et al. (2015) | |
c.139G>A | p.Glu47Lys | missense_variant | De novo | NA | - | 28554332 | Bowling KM , et al. (2017) | |
c.592G>A | p.Glu198Lys | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
c.656G>A | p.Arg219His | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
c.274G>A | p.Glu92Lys | missense_variant | De novo | NA | Simplex | 28940097 | Anazi S , et al. (2017) | |
c.145G>A | p.Glu49Lys | missense_variant | Unknown | - | Simplex | 25972378 | Loveday C , et al. (2015) | |
c.592G>A | p.Glu198Lys | missense_variant | De novo | NA | - | 29051493 | Reijnders MRF , et al. (2017) | |
c.598G>A | p.Glu200Lys | missense_variant | De novo | NA | - | 29051493 | Reijnders MRF , et al. (2017) | |
c.592G>A | p.Glu198Lys | missense_variant | De novo | NA | - | 31036916 | Lecoquierre F , et al. (2019) | |
c.592G>A | p.Glu198Lys | missense_variant | De novo | NA | Unknown | 33619735 | Brunet T et al. (2021) | |
c.1258G>A | p.Glu420Lys | missense_variant | De novo | NA | - | 29051493 | Reijnders MRF , et al. (2017) | |
c.592G>A | p.Glu198Lys | missense_variant | De novo | NA | Simplex | 29346770 | Takata A , et al. (2018) | |
c.592G>A | p.Glu198Lys | missense_variant | De novo | NA | Simplex | 33644862 | Hiraide T et al. (2021) | |
c.139G>A | p.Glu47Lys | missense_variant | De novo | NA | Simplex | 25972378 | Loveday C , et al. (2015) | |
c.598G>A | p.Glu200Lys | missense_variant | De novo | NA | Simplex | 25972378 | Loveday C , et al. (2015) | |
c.1672A>G | p.Met558Val | missense_variant | De novo | NA | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.139G>A | p.Glu47Lys | missense_variant | De novo | NA | Simplex | 27848944 | Trujillano D , et al. (2016) | |
c.545C>T | p.Thr182Met | missense_variant | Familial | Paternal | - | 28628100 | Geisheker MR , et al. (2017) | |
c.139G>A | p.Glu47Lys | missense_variant | De novo | NA | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.592G>A | p.Glu198Lys | missense_variant | De novo | NA | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.496G>A | p.Ala166Thr | missense_variant | De novo | NA | Simplex | 34580403 | Pode-Shakked B et al. (2021) | |
c.619T>A | p.Trp207Arg | missense_variant | De novo | NA | Simplex | 34580403 | Pode-Shakked B et al. (2021) | |
c.210del | p.Glu71SerfsTer9 | frameshift_variant | De novo | NA | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.592G>A | p.Glu198Lys | missense_variant | De novo | NA | Simplex | 35183220 | ÃÂlvarez-Mora MI et al. (2022) | |
c.592G>A | p.Glu198Lys | missense_variant | De novo | NA | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
c.602C>G | p.Pro201Arg | missense_variant | De novo | NA | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence


Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
Score Delta: Decreased from 4S to 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.
10/1/2021

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
7/1/2021

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
4/1/2021

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
1/1/2021

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
10/1/2020

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
7/1/2020

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
4/1/2020

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
1/1/2020

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
10/1/2019

Decreased from 4S to 1
New Scoring Scheme
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
Reports Added
[New Scoring Scheme]7/1/2019

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
4/1/2019

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
1/1/2019

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
10/1/2018

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
4/1/2018

Decreased from 4S to 4.5 + S
Description
4S
10/1/2017

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
7/1/2017

Decreased from 4S to 4S
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
4/1/2017

Decreased from 4S to 4S
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
Reports Added
[De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.2015] [B56-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]10/1/2016

Decreased from 4S to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
1/1/2016

Increased from S to 4S
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies. De novo variants in the PPP2R5D gene (one frameshift, one benign missense) have been identified in SSC probands (Iossifov et al., 2015), although no additional phenotypic information for these probands is available.
10/1/2015

Increased from to 1
Description
Four de novo missense variants in the PPP2R5D gene were identified in seven unrelated patients with developmental delay/intellectual disability; five of these patients also presented with ASD (Shang et al., 2015). Two of the de novo PPP2R5D missense variants that were found in ASD cases in this report (p.Glu198Lys and p.Glu200Lys) have been previously identified in patients with intellectual disability (Deciphering Developmental Disorders Study, 2015; Loveday et al., 2015) and have been experimentally shown to result in reduced binding to the A and C subunits of protein phosphatase 2A (Houge et al., 2015). In addition to developmental delay/intellectual disability and, in some cases, ASD, individuals with PPP2R5D mutations frequently exhibit syndromic features including overgrowth, facial dysmorphism, and additional congenital anomalies.
Krishnan Probability Score
Score 0.49218662672243
Ranking 4686/25841 scored genes
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ExAC Score
Score 0.99752007894892
Ranking 1313/18225 scored genes
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Sanders TADA Score
Score 0.46080103163505
Ranking 371/18665 scored genes
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Zhang D Score
Score 0.47404963897159
Ranking 713/20870 scored genes
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