ClinVar Miner

Submissions for variant NM_006772.3(SYNGAP1):c.3583-6G>A

dbSNP: rs869312674
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000209920 SCV000265528 uncertain significance Intellectual disability, autosomal dominant 5 2014-08-14 criteria provided, single submitter research
Diagnostic Laboratory, Strasbourg University Hospital RCV000224644 SCV000281748 pathogenic Intellectual disability 2014-07-25 criteria provided, single submitter clinical testing
Invitae RCV000209920 SCV000824390 pathogenic Intellectual disability, autosomal dominant 5 2023-11-11 criteria provided, single submitter clinical testing This sequence change falls in intron 16 of the SYNGAP1 gene. It does not directly change the encoded amino acid sequence of the SYNGAP1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with SYNGAP1-related conditions (PMID: 25167861, 28554332). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 224094). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001778797 SCV002015747 pathogenic not provided 2021-11-11 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 28524815, 28721930, 25167861, 28554332, 33639450, 34070602)
MGZ Medical Genetics Center RCV000209920 SCV002579818 likely pathogenic Intellectual disability, autosomal dominant 5 2021-12-14 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000209920 SCV003925634 uncertain significance Intellectual disability, autosomal dominant 5 2023-04-05 criteria provided, single submitter clinical testing _x000D_ Criteria applied: PS4_MOD, PM2_SUP
PreventionGenetics, part of Exact Sciences RCV004547504 SCV004106056 pathogenic SYNGAP1-related disorder 2023-05-23 criteria provided, single submitter clinical testing The SYNGAP1 c.3583-6G>A variant is predicted to interfere with splicing. This variant has been reported in the heterozygous, de novo state in an individual with intellectual disability (APN-139; Figure S8 and Table S9, Redin et al. 2014. PubMed ID: 25167861), an individual with intellectual disability (moderate), autism spectrum disorder, speech delay and seizures (Table S2, Bowling et al. 2017. PubMed ID: 28554332), and in an individual with autism, severe cognitive disability, nystagmus, feeding issues, aspecific white matter hypersignal, seizures, and no speech (Patient ID 8, Lo Barco et al. 2021. PubMed ID: 33639450). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic.

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