ClinVar Miner

Submissions for variant NM_000124.4(ERCC6):c.3259C>T (p.Arg1087Ter)

dbSNP: rs144445150
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002462394 SCV002757049 pathogenic not provided 2022-11-17 criteria provided, single submitter clinical testing Nonsense 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; This variant is associated with the following publications: (PMID: 25525159, 18628313, 29572252, 29944916, 32557569)
Labcorp Genetics (formerly Invitae), Labcorp RCV002462394 SCV003441514 pathogenic not provided 2023-08-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1800797). This premature translational stop signal has been observed in individuals with Cockayne syndrome or cerebrooculofacioskeletal syndrome (PMID: 18628313, 29572252). This variant is present in population databases (rs144445150, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Arg1087*) 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).
Lifecell International Pvt. Ltd RCV003227073 SCV003922406 likely pathogenic Cockayne syndrome type 2 criteria provided, single submitter clinical testing A Homozygote Nonsense variant c.3259C>T in Exon 18 of the ERCC6 gene that results in the amino acid substitution p.Arg1087* was identified. The observed variant has a minor allele frequency of 0.0002/0.0006% in gnomAD exomes and genomes. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. For these reasons, this variant has been classified as Likely Pathogenic.

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.