MDGA2MAM domain containing glycosylphosphatidylinositol anchor 2
Autism Reports / Total Reports
4 / 9Rare Variants / Common Variants
7 / 4Aliases
MDGA2, MAMDC1, c14_5286Associated Syndromes
-Chromosome Band
14q21.3Associated Disorders
ADHDRelevance to Autism
Rare variants in the MDGA2 gene have been identified with autism (Bucan et al., 2009). In addition, MDGA2 has been found to have genetic association with neuroticism (van den Oord et al., 2008).
Molecular Function
The encoded protein is a member of the immunoglobulin domain cell adhesion molecule subfamily and and is proposed to be involved in regulating neuronal migration and axonal guidance
External Links
SFARI Genomic Platforms
Reports related to MDGA2 (9 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Identification and characterization of two novel brain-derived immunoglobulin superfamily members with a unique structural organization | Litwack ED , et al. (2004) | No | - |
| 2 | Recent Recommendation | Genomewide association analysis followed by a replication study implicates a novel candidate gene for neuroticism | van den Oord EJ , et al. (2008) | No | - |
| 3 | Primary | Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes | Bucan M , et al. (2009) | Yes | - |
| 4 | Support | Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link with autism | Lesca G , et al. (2012) | No | ADHD |
| 5 | Support | Interaction between autism-linked MDGAs and neuroligins suppresses inhibitory synapse development | Pettem KL , et al. (2013) | No | - |
| 6 | Support | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 7 | Support | Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability | Riazuddin S , et al. (2016) | No | - |
| 8 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
| 9 | Support | Homozygous deletions implicate non-coding epigenetic marks in Autism spectrum disorder | Schmitz-Abe K et al. (2020) | Yes | - |
Rare Variants (7)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | - | - | Multiplex | 19557195 | Bucan M , et al. (2009) | |
| - | - | copy_number_loss | De novo | - | Unknown | 22738016 | Lesca G , et al. (2012) | |
| - | - | copy_number_loss | Familial | Both parents | - | 32820185 | Schmitz-Abe K et al. (2020) | |
| c.2788G>A | p.Val930Ile | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
| c.-36_-33del | - | frameshift_variant | Familial | Paternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
| c.2232A>G | p.Arg744= | splice_site_variant | Familial | Both parents | Unknown | 27457812 | Riazuddin S , et al. (2016) | |
| c.-197_-196insTGAGTGTGTTTGTGCATGAGTGTGTG | - | frameshift_variant | Familial | Maternal | Multiplex (monozygotic twins) | 31398340 | Ruzzo EK , et al. (2019) |
Common Variants (4)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.1883-5997G>A;c.1196-5997G>A;c.1886-5997G>A | - | intron_variant | - | - | - | 18762592 | van den Oord EJ , et al. (2008) | |
| c.1883-14321T>G;c.1196-14321T>G;c.1886-14321T>G | - | intron_variant | - | - | - | 18762592 | van den Oord EJ , et al. (2008) | |
| c.1883-14814G>C;c.1196-14814G>C;c.1886-14814G>C | - | intron_variant | - | - | - | 18762592 | van den Oord EJ , et al. (2008) | |
| c.2032-16192G>A;c.1345-16192G>A;c.2035-16192G>A | - | intron_variant | - | - | - | 18762592 | van den Oord EJ , et al. (2008) |
SFARI Gene score
2
Strong Candidate
Rare CNVs in the MDGA2 gene have been observed with autism (Bucan et al., 2009).
Score Delta: Score remained at 2
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
3
2
Decreased from 3 to 2
Description
Rare CNVs in the MDGA2 gene have been observed with autism (Bucan et al., 2009).
7/1/2020
3
3
Decreased from 3 to 3
Description
Rare CNVs in the MDGA2 gene have been observed with autism (Bucan et al., 2009).
10/1/2019
4
3
Decreased from 4 to 3
New Scoring Scheme
Description
Rare CNVs in the MDGA2 gene have been observed with autism (Bucan et al., 2009).
Reports Added
[New Scoring Scheme]7/1/2019
4
4
Decreased from 4 to 4
Description
Rare CNVs in the MDGA2 gene have been observed with autism (Bucan et al., 2009).
7/1/2016
4
4
Decreased from 4 to 4
Description
Rare CNVs in the MDGA2 gene have been observed with autism (Bucan et al., 2009).
1/1/2016
4
4
Decreased from 4 to 4
Description
Rare CNVs in the MDGA2 gene have been observed with autism (Bucan et al., 2009).
Reports Added
[Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes.2009] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [Genomewide association analysis followed by a replication study implicates a novel candidate gene for neuroticism.2008] [Identification and characterization of two novel brain-derived immunoglobulin superfamily members with a unique structural organization.2004] [Interaction between autism-linked MDGAs and neuroligins suppresses inhibitory synapse development.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014]7/1/2014
No data
4
Increased from No data to 4
Description
Rare CNVs in the MDGA2 gene have been observed with autism (Bucan et al., 2009).
4/1/2014
No data
4
Increased from No data to 4
Description
Rare CNVs in the MDGA2 gene have been observed with autism (Bucan et al., 2009).
Krishnan Probability Score
Score 0.49572075496372
Ranking 2830/25841 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 0.99321687136763
Ranking 1649/18225 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
Sanders TADA Score
Score 0.94918065311912
Ranking 17986/18665 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 22
Ranking 93/461 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 -0.050924634262627
Ranking 10452/20870 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.