ClinVar Miner

Submissions for variant NM_006245.4(PPP2R5D):c.751G>A (p.Asp251Asn)

dbSNP: rs1762178916
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV002249139 SCV002517377 likely pathogenic Hogue-Janssens syndrome 1 2022-05-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003094013 SCV003225759 uncertain significance not provided 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 251 of the PPP2R5D protein (p.Asp251Asn). This variant is not present in population databases (gnomAD no frequency). 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: 1685412). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant disrupts the p.Asp251 amino acid residue in PPP2R5D. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28867141, 32371413; 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.
3billion RCV002249139 SCV005328832 likely pathogenic Hogue-Janssens syndrome 1 2024-09-20 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v4.1.0 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.67 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.99 (>=0.6, sensitivity 0.72 and precision 0.9)]. Different missense changes at the same codon (p.Asp251Ala, p.Asp251His, p.Asp251Tyr, p.Asp251Val) have been reported as pathogenic/likely pathogenic with strong evidence (PMID: 28867141, 35586607, 36216457).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.