ClinVar Miner

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

dbSNP: rs1762136390
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Total submissions: 5
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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 Intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome 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 Intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome 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 Intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome 2019-02-05 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV003679050 SCV004424545 uncertain significance not provided 2023-01-15 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 982374). This variant has not been reported in the literature in individuals affected with PPP2R5D-related conditions. 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). 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.
GenomeConnect - Simons Searchlight RCV001261947 SCV001443621 pathogenic Intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome 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.

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