Submissions for variant NM_000408.5(GPD2):c.614C>T (p.Pro205Leu)

gnomAD frequency: 0.00154  dbSNP: rs142821701

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000727364	SCV000616734	uncertain significance	not provided	2017-09-19	criteria provided, single submitter	clinical testing	The P205L variant in the GPD2 gene has been reported previously in a patient with intellectual disability, mild dysmorphism, and a pervasive developmental disorder who was compound heterozygous for the P205L variant and a de novo 298 kb deletion encompassing two genes, including the GPD2 gene (Barge-Schaapveld et al., 2013). The P205L variant was also seen in the patient's healthy mother and sister, who were shown by functional studies to have reduced GPD2 activity (Barge-Schaapveld et al., 2013). The P205L variant is observed in 142/66688 (0.2%) alleles from individuals of non-Finnish European background in the ExAC dataset, and in 1 homozygous presumably healthy individual undergoing testing at GeneDx (Lek et al., 2016). The P205L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P205L as a variant of uncertain significance.
Eurofins Ntd Llc (ga)	RCV000727364	SCV000707879	uncertain significance	not provided	2017-04-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000727364	SCV005074373	benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	GPD2: BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000727364	SCV005187964	uncertain significance	not provided		criteria provided, single submitter	not provided