ClinVar Miner

Submissions for variant NM_001017420.3(ESCO2):c.294_297del (p.Arg99fs)

dbSNP: rs80359845
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized 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, University Medical Centre Ljubljana 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, Revvity RCV001054606 SCV003830718 likely pathogenic not provided 2022-03-23 criteria provided, single submitter clinical testing
GeneReviews RCV000020404 SCV000040801 not provided Roberts-SC phocomelia syndrome no assertion provided literature only

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.