ClinVar Miner

Submissions for variant NM_018699.4(PRDM5):c.247C>T (p.Arg83Cys)

gnomAD frequency: 0.00002  dbSNP: rs761027478
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Medical Genetics Ghent, University of Ghent RCV001260237 SCV001437205 pathogenic Brittle cornea syndrome 2 2020-08-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV003166589 SCV003913020 uncertain significance Cardiovascular phenotype 2022-11-04 criteria provided, single submitter clinical testing The p.R83C variant (also known as c.247C>T), located in coding exon 3 of the PRDM5 gene, results from a C to T substitution at nucleotide position 247. The arginine at codon 83 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in a homozygous state in a subject with features of brittle cornea syndrome (Dhooge T et al. Hum Mutat, 2021 06;42:711-730). This alteration has also been reported in a brittle cornea syndrome cohort (Porter LF et al. Hum Mol Genet, 2015 Dec;24:6565-79). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV004699242 SCV005201192 likely pathogenic not provided 2023-12-01 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect on protein function (PMID: 26395458); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 37710225, 33739556, 26395458)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001260237 SCV005726113 likely pathogenic Brittle cornea syndrome 2 2024-11-20 criteria provided, single submitter clinical testing Variant summary: PRDM5 c.247C>T (p.Arg83Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251280 control chromosomes (gnomAD). c.247C>T has been reported in the literature in individuals affected with Brittle cornea syndrome 2 (Porter_2015, Dhooge_2021). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding that the variant disrupts interaction with multiple PRDM5-interaction partners (Porter_2015). The following publications have been ascertained in the context of this evaluation (PMID: 26395458, 33739556). ClinVar contains an entry for this variant (Variation ID: 981044). Based on the evidence outlined above, the variant was classified as likely pathogenic.

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