Submissions for variant NM_006772.3(SYNGAP1):c.2115G>A (p.Lys705=)

dbSNP: rs1057518786

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001865299	SCV002225806	uncertain significance	Intellectual disability, autosomal dominant 5	2022-02-03	criteria provided, single submitter	clinical testing	This sequence change affects codon 705 of the SYNGAP1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SYNGAP1 protein. This variant also falls at the last nucleotide of exon 12, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SYNGAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 373940). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001865299	SCV005438489	likely pathogenic	Intellectual disability, autosomal dominant 5	2024-12-18	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000415313	SCV000492577	likely pathogenic	Global developmental delay; Stereotypic movement disorder; Delayed speech and language development; Preauricular skin tag; Generalized hypotonia	2016-05-31	no assertion criteria provided	clinical testing