ClinVar Miner

Submissions for variant NM_000124.4(ERCC6):c.3536del (p.Tyr1179fs)

gnomAD frequency: 0.00001  dbSNP: rs786205171
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Claritas Genomics RCV000170386 SCV000222804 pathogenic Cockayne syndrome type 2 2012-09-21 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224382 SCV000281408 pathogenic not provided 2015-05-14 criteria provided, single submitter clinical testing
Counsyl RCV000666242 SCV000790500 likely pathogenic DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome type 2 2017-04-03 criteria provided, single submitter clinical testing
Invitae RCV000224382 SCV001397216 pathogenic not provided 2023-12-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1179Leufs*22) in the ERCC6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC6 are known to be pathogenic (PMID: 18628313, 29572252). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Cockayne syndrome (PMID: 9443879, 19894250, 21228398, 29572252). ClinVar contains an entry for this variant (Variation ID: 190167). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003114321 SCV003800640 pathogenic Cockayne syndrome 2023-01-27 criteria provided, single submitter clinical testing Variant summary: ERCC6 c.3536delA (p.Tyr1179LeufsX22) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250950 control chromosomes (gnomAD). c.3536delA has been reported in the literature in individuals affected with Cockayne Syndrome (examples: Calmels_2018 and Mallery_1998). These data indicate that the variant is associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV000224382 SCV004169136 pathogenic not provided 2023-10-09 criteria provided, single submitter clinical testing Observed with a second variant (phase unknown) in multiple individuals with Cockayne syndrome (Mallery et al., 1998; Bell et al., 2011); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29572252, 9443879, 19894250, 21228398, 34724781)

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.