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NM_006772.3(SYNGAP1):c.2294+1G>T AND Intellectual disability, autosomal dominant 5

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 6, 2020
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:
RCV001853685.8

Allele description [Variation Report for NM_006772.3(SYNGAP1):c.2294+1G>T]

NM_006772.3(SYNGAP1):c.2294+1G>T

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.2294+1G>T
HGVS:
  • NC_000006.12:g.33441760G>T
  • NG_016137.2:g.26691G>T
  • NM_001130066.2:c.2294+1G>T
  • NM_006772.3:c.2294+1G>TMANE SELECT
  • LRG_1193t1:c.2294+1G>T
  • LRG_1193:g.26691G>T
  • NC_000006.11:g.33409537G>T
  • NM_006772.2:c.2294+1G>T
Links:
dbSNP: rs1554121970
NCBI 1000 Genomes Browser:
rs1554121970
Molecular consequence:
  • NM_001130066.2:c.2294+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_006772.3:c.2294+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002228747Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 6, 2020) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.

Hamdan FF, Daoud H, Piton A, Gauthier J, Dobrzeniecka S, Krebs MO, Joober R, Lacaille JC, Nadeau A, Milunsky JM, Wang Z, Carmant L, Mottron L, Beauchamp MH, Rouleau GA, Michaud JL.

Biol Psychiatry. 2011 May 1;69(9):898-901. doi: 10.1016/j.biopsych.2010.11.015. Epub 2011 Jan 15.

PubMed [citation]
PMID:
21237447

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002228747.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in individual(s) with clinical features of SYNGAP1-related conditions (PMID: 21237447, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 452569). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 13 of the SYNGAP1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SYNGAP1 are known to be pathogenic (PMID: 23161826, 23708187, 26989088).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024