NM_006772.3(SYNGAP1):c.2215G>T (p.Glu739Ter) AND Intellectual disability, autosomal dominant 5

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 13, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001034746.7

Allele description

NM_006772.3(SYNGAP1):c.2215G>T (p.Glu739Ter)

Genes:

SYNGAP1-AS1:SYNGAP1 antisense RNA 1 [Gene - HGNC]
SYNGAP1:synaptic Ras GTPase activating protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.32

Genomic location:

Preferred name:

NM_006772.3(SYNGAP1):c.2215G>T (p.Glu739Ter)

HGVS:

NC_000006.12:g.33441680G>T
NG_016137.2:g.26611G>T
NM_001130066.2:c.2215G>T
NM_006772.3:c.2215G>TMANE SELECT
NP_001123538.1:p.Glu739Ter
NP_006763.2:p.Glu739Ter
LRG_1193t1:c.2215G>T
LRG_1193:g.26611G>T
LRG_1193p1:p.Glu739Ter
NC_000006.11:g.33409457G>T
NM_006772.2:c.2215G>T

Protein change:

E739*

Links:

dbSNP: rs1554121934

NCBI 1000 Genomes Browser:

rs1554121934

Molecular consequence:

NM_001130066.2:c.2215G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_006772.3:c.2215G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Intellectual disability, autosomal dominant 5 (MRD5)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5
Identifiers:: MONDO: MONDO:0012960; MedGen: C2675473; OMIM: 612621

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001198041	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 13, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23161826, 23708187, 26989088, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001198041

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 13, 2019)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.

Berryer MH, Hamdan FF, Klitten LL, Møller RS, Carmant L, Schwartzentruber J, Patry L, Dobrzeniecka S, Rochefort D, Neugnot-Cerioli M, Lacaille JC, Niu Z, Eng CM, Yang Y, Palardy S, Belhumeur C, Rouleau GA, Tommerup N, Immken L, Beauchamp MH, Patel GS, Majewski J, et al.

Hum Mutat. 2013 Feb;34(2):385-94. doi: 10.1002/humu.22248. Epub 2012 Dec 12.

PubMed [citation]

PMID:: 23161826

Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, et al.

Nat Genet. 2013 Jul;45(7):825-30. doi: 10.1038/ng.2646. Epub 2013 May 26.

PubMed [citation]

PMID:: 23708187
PMCID:: PMC3704157

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001198041.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SYNGAP1 are known to be pathogenic (PMID: 23161826, 23708187, 26989088). This variant has not been reported in the literature in individuals with SYNGAP1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu739*) in the SYNGAP1 gene. It is expected to result in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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