Submissions for variant NM_006268.5(DPF2):c.899G>T (p.Arg300Leu)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV004785011	SCV005397412	likely pathogenic	Coffin-Siris syndrome 7	2023-04-14	criteria provided, single submitter	clinical testing	This sequence variant is a single nucleotide substitution (G>T) at coding position 899 of the DPF2 gene that results in an arginine to leucine amino acid change at residue 300 of the DPF2 protein. This is a novel, de novo variant that has not been previously observed in databases of clinically annotated variants (ClinVar) or in the literature in individuals with a DPF2-related illness, to our knowledge. This variant is absent from the gnomAD population database (0 of ~250,000 alleles). Bioinformatic tools produce mixed predictions as to whether this variant would be damaging or tolerated and the Arg300 residue is highly conserved across the vertebrate species examined. This variant is found in the PHD-type 1 domain, which is involved in mediating protein interactions, binding on nucleosomes, and recognizing post-translatiol histone modifications (PMID: 29429572). Studies testing the effect of this variant on protein structure or activity have not been performed, to our knowledge. Given the evidence we consider this variant to be likely pathogenic. ACMG Criteria: PM1, PM2, PS2