Submissions for variant NM_006245.4(PPP2R5D):c.752A>T (p.Asp251Val)

dbSNP: rs1064794719

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000481705	SCV000569793	likely pathogenic	not provided	2016-03-28	criteria provided, single submitter	clinical testing	The D251V variant in the PPP2R5D gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D251V variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D251V variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The D251V variant is a strong candidate for a pathogenic variant,
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV001169914	SCV001251910	pathogenic	Hogue-Janssens syndrome 1	2020-05-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000481705	SCV002194141	uncertain significance	not provided	2022-09-14	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 251 of the PPP2R5D protein (p.Asp251Val). This missense change has been observed in individual(s) with clinical features of PPP2R5D-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 420814). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant disrupts the p.Asp251 amino acid residue in PPP2R5D. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Revvity Omics, Revvity	RCV001169914	SCV003809822	uncertain significance	Hogue-Janssens syndrome 1	2021-04-08	criteria provided, single submitter	clinical testing
GenomeConnect - Simons Searchlight	RCV001169914	SCV001443623	likely pathogenic	Hogue-Janssens syndrome 1	2018-11-05	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-11-05 and interpreted as Likely Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.