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

dbSNP: rs1554121970

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520092	SCV000621386	pathogenic	not provided	2017-10-10	criteria provided, single submitter	clinical testing	The c.2294+1G>T variant in the SYNGAP1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 13. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.2294+1G>T as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001853685	SCV002228747	pathogenic	Intellectual disability, autosomal dominant 5	2020-11-06	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). 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 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).
GenomeConnect - Simons Searchlight	RCV001265155	SCV001443190	pathogenic	Complex neurodevelopmental disorder	2017-12-08	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2017-12-08 and interpreted as Pathogenic. Variant was initially reported on 2017-10-20 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.
GenomeConnect - Brain Gene Registry	RCV003987580	SCV004804597	not provided	SYNGAP1-related disorder		no assertion provided	phenotyping only	Variant classified as Pathogenic and reported on 10-20-2017 by GeneDx. 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/.