Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_206927.4(SYTL2):c.6017G>A(p.Arg2006Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000131 in 1,606,438 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
SYTL2 (HGNC:15585): (synaptotagmin like 2) The protein encoded by this gene is a synaptotagmin-like protein (SLP) that belongs to a C2 domain-containing protein family. The SLP homology domain (SHD) of this protein has been shown to specifically bind the GTP-bound form of Ras-related protein Rab-27A (RAB27A). This protein plays a role in RAB27A-dependent vesicle trafficking and controls melanosome distribution in the cell periphery. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jun 2009]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The c.3116G>A (p.R1039Q) alteration is located in exon 8 (coding exon 8) of the SYTL2 gene. This alteration results from a G to A substitution at nucleotide position 3116, causing the arginine (R) at amino acid position 1039 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -