Human Gene Module / Chromosome 2 / SNTG2

SNTG2syntrophin gamma 2

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
5 / 0
Aliases
SNTG2, G2SYN,  MGC133174,  SYN5
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
2p25.3
Associated Disorders
-
Relevance to Autism

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (Rosenfeld et al., 2010). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (Talkowski et al., 2012).

Molecular Function

his gene encodes a protein belonging to the syntrophin family. Syntrophins are cytoplasmic peripheral membrane proteins that bind to components of mechanosenstive sodium channels and the extreme carboxy-terminal domain of dystrophin and dystrophin-related proteins. The PDZ domain of this protein product interacts with a protein component of a mechanosensitive sodium channel that affects channel gating. Absence or reduction of this protein product has been associated with Duchenne muscular dystrophy.

Reports related to SNTG2 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Neuroligins 3 and 4X interact with syntrophin-gamma2, and the interactions are affected by autism-related mutations. Yamakawa H , et al. (2007) No -
2 Primary Copy number variations associated with autism spectrum disorders contribute to a spectrum of neurodevelopmental disorders. Rosenfeld JA , et al. (2010) Yes -
3 Recent Recommendation Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Talkowski ME , et al. (2012) Yes -
4 Support Identification of rare copy number variants in high burden schizophrenia families. Van Den Bossche MJ , et al. (2013) No -
5 Support Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations. Toma C , et al. (2013) Yes -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks. Ruzzo EK , et al. (2019) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation Unknown - - 22521361 Talkowski ME , et al. (2012)
- - copy_number_loss Familial Maternal Simplex 20808228 Rosenfeld JA , et al. (2010)
- - copy_number_gain Familial Paternal Multiplex 23505263 Van Den Bossche MJ , et al. (2013)
c.1273C>T p.Gln425Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1115T>C p.Leu372Ser missense_variant Familial Maternal Multiplex 23999528 Toma C , et al. (2013)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (PMID 20808228). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (PMID 22521361).

Score Delta: Score remained at 4

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (PMID 20808228). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (PMID 22521361).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (PMID 20808228). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (PMID 22521361).

7/1/2014
No data
icon
4

Increased from No data to 4

Description

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (PMID 20808228). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (PMID 22521361).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (PMID 20808228). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (PMID 22521361).

Krishnan Probability Score

Score 0.49532960903435

Ranking 3044/25841 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 9.1760883234385E-7

Ranking 15055/18225 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 0.93806249011806

Ranking 13735/18665 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 8

Ranking 236/461 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 0.11926285572312

Ranking 5740/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
EPSTI1 Epithelial-stromal interaction protein 1 Human Protein Binding 94240 Q96J88-2
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