Submissions for variant NM_006245.4(PPP2R5D):c.632A>C (p.Gln211Pro)

dbSNP: rs1762136390

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV001261947	SCV001439298	likely pathogenic	Hogue-Janssens syndrome 1	2020-06-10	criteria provided, single submitter	clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV001261947	SCV001445890	pathogenic	Hogue-Janssens syndrome 1	2019-07-09	criteria provided, single submitter	clinical testing	This variant has not been previously reported or functionally characterized in the literature to our knowledge. It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.632A>C (p.Gln211Pro) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. It localizes to the B56δ regulatory subunit in the PPP2R5D protein in close proximity to other previously reported Pathogenic variants (PMID: 26168268). Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.632A>C (p.Gln211Pro) variant is classified as Pathogenic.
Baylor Genetics	RCV001261947	SCV001521017	likely pathogenic	Hogue-Janssens syndrome 1	2019-02-05	criteria provided, single submitter	clinical testing	This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp	RCV003679050	SCV004424545	uncertain significance	not provided	2023-01-15	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 211 of the PPP2R5D protein (p.Gln211Pro). This variant has not been reported in the literature in individuals affected with PPP2R5D-related conditions. ClinVar contains an entry for this variant (Variation ID: 982374). 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. 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.
Center for Molecular Medicine, Children’s Hospital of Fudan University	RCV001261947	SCV005046473	pathogenic	Hogue-Janssens syndrome 1	2023-09-20	criteria provided, single submitter	clinical testing
GenomeConnect - Simons Searchlight	RCV001261947	SCV001443621	pathogenic	Hogue-Janssens syndrome 1	2018-08-13	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-08-13 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.