Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000020404 | SCV000245605 | pathogenic | Roberts-SC phocomelia syndrome | 2014-09-05 | criteria provided, single submitter | clinical testing | The p.Arg99SerfsX2 variant in ESCO2 has been reported in 1 individual with Roberts syndrome (Gordillo 2008), and data from large population studies is insufficient to assess the frequency of this variant. This frameshift variant is predicted to alter the protein’s amino acid sequence beginning at position 99 and lead to a premature termination codon 2 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss-of-function variants in ESCO2 have been shown to cause Roberts syndrome. In summary, this variant meets our criteria to be classified as pathogenic for Roberts syndrome acting in a recessive manner. |
Invitae | RCV001054606 | SCV001218950 | pathogenic | not provided | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg99Serfs*2) in the ESCO2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ESCO2 are known to be pathogenic (PMID: 15821733, 16380922). This variant is present in population databases (rs754138353, gnomAD 0.05%). This premature translational stop signal has been observed in individual(s) with Roberts syndrome (PMID: 18411254). ClinVar contains an entry for this variant (Variation ID: 21242). For these reasons, this variant has been classified as Pathogenic. |
Centre for Mendelian Genomics, |
RCV000020404 | SCV001370116 | pathogenic | Roberts-SC phocomelia syndrome | 2019-01-10 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2. This variant was detected in homozygous state. |
Revvity Omics, |
RCV001054606 | SCV003830718 | likely pathogenic | not provided | 2022-03-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000020404 | SCV000040801 | not provided | Roberts-SC phocomelia syndrome | no assertion provided | literature only |