ClinVar Miner

Submissions for variant NM_018699.4(PRDM5):c.248G>A (p.Arg83His)

gnomAD frequency: 0.00012  dbSNP: rs201945549
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523313 SCV000618219 uncertain significance not provided 2018-12-31 criteria provided, single submitter clinical testing The R83H variant of uncertain significance in the PRDM5 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, this variant has also been identified in conjunction with additional cardiogenetic variants in individuals referred for connective tissue disorder genetic testing at GeneDx. So far, segregation data is absent for these individuals. The R83H variant is observed in 8/126550 (0.01%) alleles from individuals of European (Non-Finnish) ancestry in large population cohorts (Lek et al., 2016). This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, R83H is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, although a missense variant in the same residue in the PRDM5 gene (R83C) has been reported in the Human Gene Mutation Database in association with brittle cornea syndrome (Stenson et al., 2014), the pathogenicity of this variant has not been definitively determined.
Invitae RCV000523313 SCV002189724 uncertain significance not provided 2022-07-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 83 of the PRDM5 protein (p.Arg83His). This variant is present in population databases (rs201945549, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PRDM5-related conditions. ClinVar contains an entry for this variant (Variation ID: 449806). 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.
Ambry Genetics RCV002431481 SCV002742830 uncertain significance Cardiovascular phenotype 2023-12-27 criteria provided, single submitter clinical testing The c.248G>A (p.R83H) alteration is located in exon 3 (coding exon 3) of the PRDM5 gene. This alteration results from a G to A substitution at nucleotide position 248, causing the arginine (R) at amino acid position 83 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002490906 SCV002791769 uncertain significance Brittle cornea syndrome 2 2022-05-12 criteria provided, single submitter clinical testing

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.