Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005419233 | SCV006087462 | uncertain significance | not specified | 2025-05-23 | criteria provided, single submitter | clinical testing | Variant summary: PRDM5 c.740C>T (p.Ser247Leu) results in a non-conservative amino acid change in the encoded protein sequence. 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. The variant allele was found at a frequency of 0.00018 in 251404 control chromosomes, predominantly at a frequency of 0.0012 within the Latino subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in PRDM5 causing Brittle cornea syndrome 2, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.740C>T in individuals affected with Brittle cornea syndrome 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1359408). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV004988808 | SCV005480477 | benign | Cardiovascular phenotype | 2024-09-16 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Breakthrough Genomics, |
RCV001872249 | SCV005190246 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
| Gene |
RCV001872249 | SCV003840869 | uncertain significance | not provided | 2024-05-01 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
| Fulgent Genetics, |
RCV002482495 | SCV002783770 | uncertain significance | Brittle cornea syndrome 2 | 2022-01-18 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001872249 | SCV002117820 | uncertain significance | not provided | 2024-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 247 of the PRDM5 protein (p.Ser247Leu). This variant is present in population databases (rs187637689, gnomAD 0.1%). 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: 1359408). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |