MAGEL2MAGE-like 2
Autism Reports / Total Reports
3 / 26Rare Variants / Common Variants
50 / 0Aliases
MAGEL2, NDNL1, nM15Associated Syndromes
Schaaf-Yang syndrome, Chitayat-Hall syndrome, Schaaf-Yang syndrome, DD, Schaaf-Yang syndrome, Prader-Willi syndromeChromosome Band
15q11.2Associated Disorders
DD/NDD, ADHD, ID, EPS, ASDRelevance to Autism
Truncating variants on the paternal allele of the MAGEL2 gene were identified in four individuals presenting with autism spectrum disorder (ASD), intellectual disability and a varying degree of clinical and behavioral features of Prader-Willi syndrome (PWS) (Schaaf et al., 2013).
Molecular Function
The protein encoded by this paternally-imprinted gene may enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases and has been proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. This gene may play a role in Prader-Willi syndrome (PWS, OMIM 176270), a contiguous gene syndrome characterized by muscular hypotonia, mental retardation, short stature, obesity, hypogonadotropic hypogonadism, and small hands and feet that results from inactivity of the paternal copies of a number of genes on 15q11, through deletion or disruption of these genes or maternal uniparental disomy 15.
External Links
SFARI Genomic Platforms
Reports related to MAGEL2 (26 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Primary | Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism | Schaaf CP , et al. (2013) | No | ASD, ID |
2 | Support | Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders | Soden SE , et al. (2014) | No | DD, ASD |
3 | Recent Recommendation | Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis | Mejlachowicz D , et al. (2015) | No | - |
4 | Recent Recommendation | The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families | Fountain MD , et al. (2016) | No | DD, ID, ASD, epilepsy/seizures |
5 | Recent Recommendation | Loss of Magel2 impairs the development of hypothalamic Anorexigenic circuits | Maillard J , et al. (2016) | No | - |
6 | Support | Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability | Lelieveld SH et al. (2016) | No | - |
7 | Support | Clinical exome sequencing: results from 2819 samples reflecting 1000 families | Trujillano D , et al. (2016) | No | DD, microcephaly |
8 | Support | A De Novo Nonsense Mutation in MAGEL2 in a Patient Initially Diagnosed as Opitz-C: Similarities Between Schaaf-Yang and Opitz-C Syndromes | Urreizti R , et al. (2017) | No | Features of Opitz trigonocephaly C syndrome, ID |
9 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay | Bowling KM , et al. (2017) | No | - |
10 | Support | Pitfalls of trio-based exome sequencing: imprinted genes and parental mosaicism-MAGEL2 as an example | Palomares-Bralo M , et al. (2017) | No | DD |
11 | Support | Three patients with Schaaf-Yang syndrome exhibiting arthrogryposis and endocrinological abnormalities | Enya T , et al. (2018) | No | Autistic behavior |
12 | Support | Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the phenotype of MAGEL2-related disorders | Jobling R , et al. (2018) | No | ASD |
13 | Recent Recommendation | Schaaf-Yang syndrome overview: Report of 78 individuals | McCarthy J , et al. (2018) | No | ASD |
14 | Support | A Novel Mutation of MAGEL2 in a Patient with Schaaf-Yang Syndrome and Hypopituitarism | D Hidalgo-Santos A , et al. (2018) | No | ASD |
15 | Support | Neurocognitive and Neurobehavioral Phenotype of Youth with Schaaf-Yang Syndrome | Thomason MM , et al. (2018) | No | ASD |
16 | Support | MAGEL2-related disorders: A study and case series | Patak J , et al. (2019) | No | ASD, ADHD |
17 | Support | The adult phenotype of Schaaf-Yang syndrome | Marbach F et al. (2020) | No | ASD |
18 | Support | - | Ahn H et al. (2020) | No | ASD or autistic features, epilepsy/seizures |
19 | Support | - | Duan Y et al. (2021) | No | DD, ID, autistic features |
20 | Support | - | Bosque Ortiz GM et al. (2021) | No | - |
21 | Support | - | Woodbury-Smith M et al. (2022) | Yes | - |
22 | Support | - | Negishi Y et al. (2022) | No | ASD |
23 | Support | - | Yuan B et al. (2023) | Yes | - |
24 | Support | - | Sheth F et al. (2023) | Yes | DD, ID, epilepsy/seizures |
25 | Support | - | Tamam Khalaf et al. (2024) | No | - |
26 | Recent recommendation | - | David Heimdörfer et al. (2024) | No | - |
Rare Variants (50)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.1687C>T | p.Gln563Ter | stop_gained | Unknown | - | - | 34128869 | Duan Y et al. (2021) | |
c.2874G>A | p.Trp958Ter | stop_gained | De novo | - | - | 33076953 | Marbach F et al. (2020) | |
c.1354C>T | p.Arg452Cys | missense_variant | De novo | - | - | 36881370 | Yuan B et al. (2023) | |
c.3124C>T | p.Gln1042Ter | stop_gained | De novo | - | - | 24076603 | Schaaf CP , et al. (2013) | |
c.3208G>T | p.Glu1070Ter | stop_gained | De novo | - | - | 28554332 | Bowling KM , et al. (2017) | |
c.1912C>T | p.Gln638Ter | stop_gained | De novo | - | - | 27195816 | Fountain MD , et al. (2016) | |
c.2873G>A | p.Trp958Ter | stop_gained | Unknown | - | - | 27195816 | Fountain MD , et al. (2016) | |
c.3131C>A | p.Ser1044Ter | stop_gained | De novo | - | Simplex | 29359444 | Enya T , et al. (2018) | |
c.3169G>T | p.Glu1057Ter | stop_gained | De novo | - | Simplex | 31397880 | Patak J , et al. (2019) | |
c.1819C>T | p.Gln607Ter | stop_gained | Familial | Paternal | - | 33076953 | Marbach F et al. (2020) | |
c.1912C>T | p.Gln638Ter | stop_gained | De novo | - | Simplex | 28281571 | Urreizti R , et al. (2017) | |
c.1996dup | p.Gln666ProfsTer47 | frameshift_variant | De novo | - | - | 33371171 | Ahn H et al. (2020) | |
c.1762C>T | p.Gln588Ter | stop_gained | Unknown | - | Multiplex | 29599419 | Jobling R , et al. (2018) | |
c.1996dupC | p.Gln666fs | frameshift_variant | De novo | - | - | 27195816 | Fountain MD , et al. (2016) | |
c.3019C>T | p.Gln1007Ter | stop_gained | De novo | - | - | 30323850 | D Hidalgo-Santos A , et al. (2018) | |
c.1621C>T | p.Gln541Ter | stop_gained | Familial | Paternal | - | 27195816 | Fountain MD , et al. (2016) | |
c.1996dup | p.Gln666ProfsTer47 | frameshift_variant | De novo | - | - | 31397880 | Patak J , et al. (2019) | |
c.2958del | p.Ser987AlafsTer5 | frameshift_variant | De novo | - | - | 33076953 | Marbach F et al. (2020) | |
c.3235G>T | p.Glu1079Ter | stop_gained | Familial | Paternal | - | 27195816 | Fountain MD , et al. (2016) | |
c.2821dup | p.Arg941ProfsTer10 | frameshift_variant | Unknown | - | - | 33076953 | Marbach F et al. (2020) | |
c.1790del | p.Pro597HisfsTer105 | frameshift_variant | Unknown | - | - | 33076953 | Marbach F et al. (2020) | |
c.1800del | p.Pro601GlnfsTer101 | frameshift_variant | De novo | - | - | 33076953 | Marbach F et al. (2020) | |
c.3288T>C | p.His1096%3D | synonymous_variant | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
c.1912C>T | p.Gln638Ter | stop_gained | Familial | Paternal | Multiplex | 29359444 | Enya T , et al. (2018) | |
c.2217del | p.Lys740ArgfsTer11 | frameshift_variant | De novo | - | Simplex | 33371171 | Ahn H et al. (2020) | |
c.1996dup | p.Gln666ProfsTer47 | frameshift_variant | De novo | - | - | 27479843 | Lelieveld SH et al. (2016) | |
c.1580del | p.Pro527ArgfsTer175 | frameshift_variant | Unknown | - | - | 27195816 | Fountain MD , et al. (2016) | |
c.1996dupC | p.Gln666ProfsTer47 | frameshift_variant | Familial | Paternal | - | 33371171 | Ahn H et al. (2020) | |
c.1613C>A | p.Ala538Glu | missense_variant | Familial | Paternal | Simplex | 31397880 | Patak J , et al. (2019) | |
c.3122del | p.Val1041AlafsTer7 | frameshift_variant | De novo | - | Simplex | 31397880 | Patak J , et al. (2019) | |
c.3181_3182del | p.Ile1061HisfsTer7 | frameshift_variant | De novo | - | - | 24076603 | Schaaf CP , et al. (2013) | |
c.1930C>G | p.Gln644Glu | missense_variant | Unknown | - | Extended multiplex | 37543562 | Sheth F et al. (2023) | |
c.2179_2180del | p.Asp727ProfsTer6 | frameshift_variant | - | - | Multiplex | 29599419 | Jobling R , et al. (2018) | |
c.1652del | p.Val551AspfsTer151 | frameshift_variant | De novo | - | Simplex | 24076603 | Schaaf CP , et al. (2013) | |
c.1801_1802del | p.Pro601AsnfsTer111 | frameshift_variant | Unknown | - | - | 27195816 | Fountain MD , et al. (2016) | |
c.1996dupC | p.Gln666ProfsTer47 | frameshift_variant | De novo | - | Multiplex | 25473036 | Soden SE , et al. (2014) | |
c.1996dup | p.Gln666ProfsTer47 | frameshift_variant | De novo | - | Simplex | 27848944 | Trujillano D , et al. (2016) | |
- | - | complex_structural_alteration | Familial | Paternal | Multi-generational | 29599419 | Jobling R , et al. (2018) | |
c.2118del | p.Leu708TrpfsTer7 | frameshift_variant | De novo | - | Simplex | 26365340 | Mejlachowicz D , et al. (2015) | |
c.1802del | p.Pro601GlnfsTer101 | frameshift_variant | Unknown | Not maternal | - | 24076603 | Schaaf CP , et al. (2013) | |
c.1996dupC | p.Gln666fs | frameshift_variant | Familial | Paternal | Multiplex | 27195816 | Fountain MD , et al. (2016) | |
c.3449_3450del | p.Phe1150TrpfsTer4 | frameshift_variant | Familial | Paternal | Simplex | 33371171 | Ahn H et al. (2020) | |
c.1996dup | p.Gln666ProfsTer47 | frameshift_variant | Familial | Paternal | Simplex | 29599419 | Jobling R , et al. (2018) | |
c.1158_1161del | p.Thr388GlyfsTer48 | frameshift_variant | Unknown | - | Multiplex | 38438125 | Tamam Khalaf et al. (2024) | |
c.1996_1997insCA | p.Gln666ProfsTer37 | frameshift_variant | Familial | Paternal | Simplex | 31397880 | Patak J , et al. (2019) | |
c.1996dupC | p.Gln666fs | frameshift_variant | Familial | Paternal | Extended multiplex | 27195816 | Fountain MD , et al. (2016) | |
c.1996del | p.Gln666SerfsTer36 | frameshift_variant | Familial | Paternal | Multiplex | 26365340 | Mejlachowicz D , et al. (2015) | |
c.1996dup | p.Gln666ProfsTer47 | frameshift_variant | Familial | Paternal | Simplex | 28640240 | Palomares-Bralo M , et al. (2017) | |
c.1996dup | p.Gln666ProfsTer47 | frameshift_variant | Familial | Paternal | Extended multiplex | 27195816 | Fountain MD , et al. (2016) | |
c.2170_2171insTCTTCTATAGACCGCAGGGGCTCCTCTAAAGAGCGCAGGACCTCCTCGAAGGAGCGCAGGGCC | p.Ser724delinsPhePheTyrArgProGlnGlyLeuLeuTer | inframe_insertion | Unknown | - | - | 33076953 | Marbach F et al. (2020) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence, Syndromic
Score Delta: Score remained at 1S
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.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
1/1/2021
Score remained at 1
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603). A frameshift variant in MAGEL2 (c.1996dupC;p.Gln666ProfsTer47) was identified in two siblings presenting with Schaaf-Yang syndrome, one of whom was diagnosed with ASD; this variant was undetectable in DNA from the blood of either parent, suggesting gonadal mosaicism of this paternally expressed gene (Soden et al., 2014). Fountain et al., 2016 reported a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families. Of the seven newly identified cases in Fountain et al., 2016 that were formally evaluated for ASD, four cases were formally diagnosed with ASD (including two paternal cousins with a paternally-inherited frameshift variant and a case with a de novo frameshift variant); an additional six cases presented with autistic behaviors but were not formally evaluated for ASD. McCarthy et al., 2018 reported the phenotypes of an international cohort of 78 patients with nonsense or frameshift mutations in MAGEL2 (43 previously reported individuals, 35 newly identified individuals) and found that, of the 32 individuals in this cohort that had been formally evaluated for ASD using ADOS-2 and ADI-R, 25 were formally diagnosed with ASD (78%).
10/1/2020
Score remained at 1
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603). A frameshift variant in MAGEL2 (c.1996dupC;p.Gln666ProfsTer47) was identified in two siblings presenting with Schaaf-Yang syndrome, one of whom was diagnosed with ASD; this variant was undetectable in DNA from the blood of either parent, suggesting gonadal mosaicism of this paternally expressed gene (Soden et al., 2014). Fountain et al., 2016 reported a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families. Of the seven newly identified cases in Fountain et al., 2016 that were formally evaluated for ASD, four cases were formally diagnosed with ASD (including two paternal cousins with a paternally-inherited frameshift variant and a case with a de novo frameshift variant); an additional six cases presented with autistic behaviors but were not formally evaluated for ASD. McCarthy et al., 2018 reported the phenotypes of an international cohort of 78 patients with nonsense or frameshift mutations in MAGEL2 (43 previously reported individuals, 35 newly identified individuals) and found that, of the 32 individuals in this cohort that had been formally evaluated for ASD using ADOS-2 and ADI-R, 25 were formally diagnosed with ASD (78%).
Reports Added
[The adult phenotype of Schaaf-Yang syndrome2020]10/1/2019
Decreased from 2S to 1
New Scoring Scheme
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603). A frameshift variant in MAGEL2 (c.1996dupC;p.Gln666ProfsTer47) was identified in two siblings presenting with Schaaf-Yang syndrome, one of whom was diagnosed with ASD; this variant was undetectable in DNA from the blood of either parent, suggesting gonadal mosaicism of this paternally expressed gene (Soden et al., 2014). Fountain et al., 2016 reported a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families. Of the seven newly identified cases in Fountain et al., 2016 that were formally evaluated for ASD, four cases were formally diagnosed with ASD (including two paternal cousins with a paternally-inherited frameshift variant and a case with a de novo frameshift variant); an additional six cases presented with autistic behaviors but were not formally evaluated for ASD. McCarthy et al., 2018 reported the phenotypes of an international cohort of 78 patients with nonsense or frameshift mutations in MAGEL2 (43 previously reported individuals, 35 newly identified individuals) and found that, of the 32 individuals in this cohort that had been formally evaluated for ASD using ADOS-2 and ADI-R, 25 were formally diagnosed with ASD (78%).
Reports Added
[New Scoring Scheme]7/1/2019
Decreased from 2S to 2S
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603). A frameshift variant in MAGEL2 (c.1996dupC;p.Gln666ProfsTer47) was identified in two siblings presenting with Schaaf-Yang syndrome, one of whom was diagnosed with ASD; this variant was undetectable in DNA from the blood of either parent, suggesting gonadal mosaicism of this paternally expressed gene (Soden et al., 2014). Fountain et al., 2016 reported a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families. Of the seven newly identified cases in Fountain et al., 2016 that were formally evaluated for ASD, four cases were formally diagnosed with ASD (including two paternal cousins with a paternally-inherited frameshift variant and a case with a de novo frameshift variant); an additional six cases presented with autistic behaviors but were not formally evaluated for ASD. McCarthy et al., 2018 reported the phenotypes of an international cohort of 78 patients with nonsense or frameshift mutations in MAGEL2 (43 previously reported individuals, 35 newly identified individuals) and found that, of the 32 individuals in this cohort that had been formally evaluated for ASD using ADOS-2 and ADI-R, 25 were formally diagnosed with ASD (78%).
Reports Added
[MAGEL2-related disorders: A study and case series.2019]10/1/2018
Decreased from 2S to 2S
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603). A frameshift variant in MAGEL2 (c.1996dupC;p.Gln666ProfsTer47) was identified in two siblings presenting with Schaaf-Yang syndrome, one of whom was diagnosed with ASD; this variant was undetectable in DNA from the blood of either parent, suggesting gonadal mosaicism of this paternally expressed gene (Soden et al., 2014). Fountain et al., 2016 reported a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families. Of the seven newly identified cases in Fountain et al., 2016 that were formally evaluated for ASD, four cases were formally diagnosed with ASD (including two paternal cousins with a paternally-inherited frameshift variant and a case with a de novo frameshift variant); an additional six cases presented with autistic behaviors but were not formally evaluated for ASD. McCarthy et al., 2018 reported the phenotypes of an international cohort of 78 patients with nonsense or frameshift mutations in MAGEL2 (43 previously reported individuals, 35 newly identified individuals) and found that, of the 32 individuals in this cohort that had been formally evaluated for ASD using ADOS-2 and ADI-R, 25 were formally diagnosed with ASD (78%).
7/1/2017
Decreased from 2S to 2S
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603). A frameshift variant in MAGEL2 (c.1996dupC;p.Gln666ProfsTer47) was identified in two siblings presenting with Schaaf-Yang syndrome, one of whom was diagnosed with ASD; this variant was undetectable in DNA from the blood of either parent, suggesting gonadal mosaicism of this paternally expressed gene (Soden et al., 2014). Fountain et al., 2016 reported a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families. Of the seven newly identified cases in Fountain et al., 2016 that were formally evaluated for ASD, four cases were formally diagnosed with ASD (including two paternal cousins with a paternally-inherited frameshift variant and a case with a de novo frameshift variant); an additional six cases presented with autistic behaviors but were not formally evaluated for ASD.
4/1/2017
Decreased from 2S to 2S
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603). A frameshift variant in MAGEL2 (c.1996dupC;p.Gln666ProfsTer47) was identified in two siblings presenting with Schaaf-Yang syndrome, one of whom was diagnosed with ASD; this variant was undetectable in DNA from the blood of either parent, suggesting gonadal mosaicism of this paternally expressed gene (Soden et al., 2014). Fountain et al., 2016 reported a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families. Of the seven newly identified cases in Fountain et al., 2016 that were formally evaluated for ASD, four cases were formally diagnosed with ASD (including two paternal cousins with a paternally-inherited frameshift variant and a case with a de novo frameshift variant); an additional six cases presented with autistic behaviors but were not formally evaluated for ASD.
Reports Added
[Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism.2013] [Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis.2015] [The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families.2016] [Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.2014] [Loss of Magel2 impairs the development of hypothalamic Anorexigenic circuits.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [A De Novo Nonsense Mutation in MAGEL2 in a Patient Initially Diagnosed as Opitz-C: Similarities Between Schaaf-Yang and Opitz-C Syndromes.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]10/1/2016
Decreased from 2S to 2S
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603). A frameshift variant in MAGEL2 (c.1996dupC;p.Gln666ProfsTer47) was identified in two siblings presenting with Schaaf-Yang syndrome, one of whom was diagnosed with ASD; this variant was undetectable in DNA from the blood of either parent, suggesting gonadal mosaicism of this paternally expressed gene (Soden et al., 2014). Fountain et al., 2016 reported a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families. Of the seven newly identified cases in Fountain et al., 2016 that were formally evaluated for ASD, four cases were formally diagnosed with ASD (including two paternal cousins with a paternally-inherited frameshift variant and a case with a de novo frameshift variant); an additional six cases presented with autistic behaviors but were not formally evaluated for ASD.
7/1/2016
Decreased from 2S to 2S
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603). A frameshift variant in MAGEL2 (c.1996dupC;p.Gln666ProfsTer47) was identified in two siblings presenting with Schaaf-Yang syndrome, one of whom was diagnosed with ASD; this variant was undetectable in DNA from the blood of either parent, suggesting gonadal mosaicism of this paternally expressed gene (Soden et al., 2014). Fountain et al., 2016 reported a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families. Of the seven newly identified cases in Fountain et al., 2016 that were formally evaluated for ASD, four cases were formally diagnosed with ASD (including two paternal cousins with a paternally-inherited frameshift variant and a case with a de novo frameshift variant); an additional six cases presented with autistic behaviors but were not formally evaluated for ASD.
4/1/2016
Decreased from 2S to 2S
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603). A frameshift variant in MAGEL2 (c.1996dupC;p.Gln666ProfsTer47) was identified in two siblings presenting with Schaaf-Yang syndrome, one of whom was diagnosed with ASD; this variant was undetectable in DNA from the blood of either parent, suggesting gonadal mosaicism of this paternally expressed gene (Soden et al., 2014). Fountain et al., 2016 reported a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families. Of the seven newly identified cases in Fountain et al., 2016 that were formally evaluated for ASD, four cases were formally diagnosed with ASD (including two paternal cousins with a paternally-inherited frameshift variant and a case with a de novo frameshift variant); an additional six cases presented with autistic behaviors but were not formally evaluated for ASD.
Reports Added
[Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism.2013] [Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis.2015] [The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families.2016] [Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.2014]1/1/2016
Decreased from 2S to 2S
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603).
4/1/2015
Increased from to 2S
Description
A de novo frameshift variant on the paternal allele of the MAGEL2 gene was identified in a male patient with ASD, mild intellectual disability, and a history of Prader-Willi-like phenotypes; this variant was absent in dbSNP, 1000 Genomes, and ESP5000 . A search of the Baylor College of Medicine Whole-Genome Laboratory database identified an additional three subjects with loss-of-function variants on the paternal allele of MAGEL2 (two of which were de novo) who also presented with ASD, intellectual disability, and some or all of the clinical and behavioral features of Prader-Willi syndrome (PMID 24076603).
Krishnan Probability Score
Score 0.60479047652504
Ranking 343/25841 scored genes
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ExAC Score
Score 0.92241126903557
Ranking 3010/18225 scored genes
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Sanders TADA Score
Score 0.93464987434279
Ranking 12633/18665 scored genes
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Larsen Cumulative Evidence Score
Score 38
Ranking 54/461 scored genes
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Zhang D Score
Score 0.14940069206688
Ranking 5189/20870 scored genes
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CNVs associated with MAGEL2(1 CNVs)
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15q11.2 | 122 | Deletion-Duplication | 161 / 2259 |