Submissions for variant NM_020631.5(PLEKHG5):c.2485G>T (p.Asp829Tyr) (rs200162521)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522669	SCV000619856	uncertain significance	not provided	2017-08-11	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the PLEKHG5 gene. The c.2485 G>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D829Y variant is observed in 26/6964 (0.4%) alleles from individuals of East Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.2485 G>T may increase the strength of the cryptic splice acceptor site in exon 20. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. If c.2485 G>T does not alter splicing, it will result in the D829Y missense change, which is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Aspartic Acid are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina	RCV000390391	SCV000358728	uncertain significance	Distal spinal muscular atrophy	2016-06-14	criteria provided, single submitter	clinical testing