ClinVar Genomic variation as it relates to human health
NM_019066.5(MAGEL2):c.1912C>T (p.Gln638Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_019066.5(MAGEL2):c.1912C>T (p.Gln638Ter)
Variation ID: 208684 Accession: VCV000208684.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 15q11.2 15: 23645831 (GRCh38) [ NCBI UCSC ] 15: 23890978 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Sep 14, 2015 Apr 15, 2024 Apr 4, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_019066.5:c.1912C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_061939.3:p.Gln638Ter nonsense NC_000015.10:g.23645831G>A NC_000015.9:g.23890978G>A NG_016776.1:g.7016C>T LRG_1046:g.7016C>T LRG_1046t1:c.1912C>T LRG_1046p1:p.Gln638Ter - Protein change
- Q638*
- Other names
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- Canonical SPDI
- NC_000015.10:23645830:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MAGEL2 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
899 | 1198 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Sep 3, 2014 | RCV000190699.3 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 8, 2023 | RCV000238706.4 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Apr 4, 2024 | RCV000508676.14 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 31, 2018 | RCV000762935.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 20, 2023 | RCV003407693.4 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Prader-Willi syndrome
Schaaf-Yang syndrome
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893358.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(Jun 26, 2019)
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criteria provided, single submitter
Method: clinical testing
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Schaaf-Yang syndrome
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001158491.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
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Pathogenic
(May 19, 2021)
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criteria provided, single submitter
Method: clinical testing
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Schaaf-Yang syndrome
Affected status: yes
Allele origin:
paternal
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Center for Molecular Medicine, Children’s Hospital of Fudan University
Accession: SCV001622604.1
First in ClinVar: May 23, 2021 Last updated: May 23, 2021 |
Sex: female
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Pathogenic
(Oct 13, 2021)
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criteria provided, single submitter
Method: research
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Schaaf-Yang syndrome
Affected status: yes
Allele origin:
unknown
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HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: CSER-SouthSeq
Accession: SCV002012480.1 First in ClinVar: Nov 11, 2021 Last updated: Nov 11, 2021 |
Comment:
ACMG codes: PVS1; PS4M; PM2; PP5
Number of individuals with the variant: 1
Clinical Features:
Small for gestational age (present) , Micrognathia (present) , Atrial septal defect (present) , Neonatal hypoglycemia (present) , Single transverse palmar crease (present) , Joint … (more)
Small for gestational age (present) , Micrognathia (present) , Atrial septal defect (present) , Neonatal hypoglycemia (present) , Single transverse palmar crease (present) , Joint contracture of the 4th finger (present) , Hypotonia (present) , Hypernatremia (present) (less)
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Likely pathogenic
(Dec 03, 2015)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
unknown
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Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000297290.3
First in ClinVar: Jul 31, 2016 Last updated: Dec 24, 2022 |
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Pathogenic
(Sep 03, 2014)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV000244140.6
First in ClinVar: Sep 14, 2015 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Thrombocytopenia (present) , Micropenis (present) , Abnormality of the pituitary gland (present) , Flexion contracture of digit (present) , Feeding difficulties (present) , Apneic episodes … (more)
Thrombocytopenia (present) , Micropenis (present) , Abnormality of the pituitary gland (present) , Flexion contracture of digit (present) , Feeding difficulties (present) , Apneic episodes in infancy (present) , Polyhydramnios (present) , Prominent forehead (present) , Dolichocephaly (present) , Deeply set eye (present) , Shallow orbits (present) , High, narrow palate (present) , Bulbous nose (present) , Abnormality of the chin (present) , Micrognathia (present) , Sacral dimple (present) , Patent ductus arteriosus (present) , Hypercapnia (present) (less)
Sex: male
Ethnicity/Population group: Caucasian
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Pathogenic
(Apr 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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MAGEL2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004112089.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The MAGEL2 c.1912C>T variant is predicted to result in premature protein termination (p.Gln638*). This variant was reported in multiple individuals with Schaaf-Yang syndrome and de … (more)
The MAGEL2 c.1912C>T variant is predicted to result in premature protein termination (p.Gln638*). This variant was reported in multiple individuals with Schaaf-Yang syndrome and de novo occurrences have been noted in several cases (Urreizti et al. 2017. PubMed ID: 28281571; Halloun et al. 2021. PubMed ID: 34051361; Negishi et al. 2019. PubMed ID: 31791363). This variant was also reported in a patient with neonatal demise (Yang et al. 2019. PubMed ID: 31501239). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant has been interpreted as pathogenic and likely pathogenic by multiple submitters in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/208684/). Nonsense variants in MAGEL2 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Oct 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV004170148.1
First in ClinVar: Nov 25, 2023 Last updated: Nov 25, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation, as the last 612 amino acids are lost, and other loss-of-function variants have been reported downstream in … (more)
Nonsense variant predicted to result in protein truncation, as the last 612 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27195816, 31501239, 28281571, 31791363, 29359444, 34128869, 35595280, 34051361, 37404980, 33726816, 36243518) (less)
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Pathogenic
(Apr 04, 2024)
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criteria provided, single submitter
Method: clinical testing
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Schaaf-Yang syndrome
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004809925.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
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Pathogenic
(Sep 26, 2017)
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no assertion criteria provided
Method: literature only
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SCHAAF-YANG SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000605831.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
Comment on evidence:
In a 19-year-old Spanish woman (patient 7) with Schaaf-Yang syndrome (SHFYNG; 615547), Urreizti et al. (2017) identified a de novo heterozygous c.1912C-T transition in the … (more)
In a 19-year-old Spanish woman (patient 7) with Schaaf-Yang syndrome (SHFYNG; 615547), Urreizti et al. (2017) identified a de novo heterozygous c.1912C-T transition in the MAGEL2 gene, resulting in a gln638-to-ter (Q638X) substitution. Thr mutation, which was found by whole-exome sequencing, occurred on the paternal chromosome. In 1-year-old boy (patient 4) with SHFYNG, Fountain et al. (2017) identified a de novo heterozygous Q638X mutation in the MAGEL2 gene. (less)
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Pathogenic
(Jun 25, 2018)
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no assertion criteria provided
Method: clinical testing
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Schaaf-Yang syndrome
Affected status: yes
Allele origin:
unknown,
de novo
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Department Of Pediatrics And Neonatology, Nagoya City University Graduate School Of Medical Sciences
Accession: SCV000784667.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
Observation 1:
Number of individuals with the variant: 1
Age: 0-9 years
Sex: female
Ethnicity/Population group: Asian
Geographic origin: Japan
Observation 2:
Number of individuals with the variant: 1
Age: 0-9 years
Sex: male
Ethnicity/Population group: Asian
Geographic origin: Japan
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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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 | Scientific reports | 2017 | PMID: 28281571 |
The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families. | Fountain MD | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 27195816 |
Text-mined citations for rs797044883 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.