ClinVar Genomic variation as it relates to human health
NM_006772.3(SYNGAP1):c.1861C>T (p.Arg621Ter)
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_006772.3(SYNGAP1):c.1861C>T (p.Arg621Ter)
Variation ID: 411589 Accession: VCV000411589.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6p21.32 6: 33440913 (GRCh38) [ NCBI UCSC ] 6: 33408690 (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 Apr 17, 2017 Mar 30, 2024 May 5, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_006772.3:c.1861C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006763.2:p.Arg621Ter nonsense NM_001130066.2:c.1861C>T NP_001123538.1:p.Arg621Ter nonsense NC_000006.12:g.33440913C>T NC_000006.11:g.33408690C>T NG_016137.2:g.25844C>T LRG_1193:g.25844C>T LRG_1193t1:c.1861C>T LRG_1193p1:p.Arg621Ter - Protein change
- R621*
- Other names
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- Canonical SPDI
- NC_000006.12:33440912:C:T
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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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SYNGAP1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
323 | 1582 | |
SYNGAP1-AS1 | - | - | - |
GRCh38 GRCh38 |
- | 1243 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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 (4) |
criteria provided, multiple submitters, no conflicts
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Apr 1, 2023 | RCV000470395.10 | |
Pathogenic (1) |
no assertion criteria provided
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Apr 6, 2018 | RCV001265347.1 | |
Pathogenic (1) |
criteria provided, single submitter
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- | RCV002274036.2 | |
Pathogenic (1) |
criteria provided, single submitter
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May 5, 2023 | RCV003227762.1 |
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
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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
(Jul 10, 2019)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 5
Affected status: yes
Allele origin:
de novo
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Genetics Laboratory - UDIAT Centre Diagnòstic, Hospital Universitari Parc Tauli
Accession: SCV000930695.1
First in ClinVar: Aug 18, 2019 Last updated: Aug 18, 2019 |
Clinical Features:
Angelman-like syndrome (present) , auto and hetero-aggressive behavior (present)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental delay
Affected status: yes
Allele origin:
de novo
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Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille
Accession: SCV002559123.1
First in ClinVar: Aug 15, 2022 Last updated: Aug 15, 2022 |
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Pathogenic
(Sep 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 5
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Baylor Genetics
Accession: SCV000807317.2
First in ClinVar: Apr 17, 2017 Last updated: Dec 11, 2022 |
Comment:
This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory in a 7-year-old male with global … (more)
This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory in a 7-year-old male with global delays, autistic spectrum, seizure disorder, Chiari I malformation. (less)
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Pathogenic
(May 05, 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: SCV003924690.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32472547, 34653234, 33090308, 30455457, 34924933, 28191889, 31440721, 31175295, 31395010) (less)
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Pathogenic
(Apr 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 5
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000552817.6
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 411589). This variant has not been … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 411589). This variant has not been reported in the literature in individuals affected with SYNGAP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg621*) in the SYNGAP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SYNGAP1 are known to be pathogenic (PMID: 23161826, 23708187, 26989088). (less)
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Pathogenic
(Apr 06, 2018)
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no assertion criteria provided
Method: provider interpretation
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Complex neurodevelopmental disorder
Affected status: yes
Allele origin:
unknown
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GenomeConnect - Simons Searchlight
Accession: SCV001443466.1
First in ClinVar: Nov 21, 2020 Last updated: Nov 21, 2020 |
Comment:
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-04-06 and interpreted as Pathogenic. The reporting laboratory … (more)
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-04-06 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight. (less)
Observation 1:
Number of individuals with the variant: 1
Sex: male
Testing laboratory: MedGenome Labs Ltd
Date variant was reported to submitter: 2018-03-22
Testing laboratory interpretation: Pathogenic
Observation 2:
Number of individuals with the variant: 1
Sex: male
Testing laboratory: Baylor Genetics
Date variant was reported to submitter: 2013-08-23
Testing laboratory interpretation: Pathogenic
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not provided
(-)
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no classification provided
Method: phenotyping only
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Intellectual disability, autosomal dominant 5
Affected status: yes
Allele origin:
unknown
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GenomeConnect - Brain Gene Registry
Accession: SCV004804631.1
First in ClinVar: Mar 30, 2024 Last updated: Mar 30, 2024 |
Comment:
Variant classified as Pathogenic and reported on 03-22-2018 by MedGenome. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does … (more)
Variant classified as Pathogenic and reported on 03-22-2018 by MedGenome. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. (less)
Clinical Features:
Microcephaly (present) , Global developmental delay (present) , Atypical absence seizure (present)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: male
Method: Exome Sequencing
Testing laboratory: MedGenome Laboratories
Date variant was reported to submitter: 2018-03-22
Testing laboratory interpretation: Pathogenic
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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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Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy. | Mignot C | Journal of medical genetics | 2016 | PMID: 26989088 |
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. | Carvill GL | Nature genetics | 2013 | PMID: 23708187 |
Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency. | Berryer MH | Human mutation | 2013 | PMID: 23161826 |
Text-mined citations for rs1060503386 ...
HelpRecord last updated Sep 29, 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.