ClinVar Miner

Submissions for variant NM_000124.4(ERCC6):c.2569C>T (p.Arg857Ter)

gnomAD frequency: 0.00001  dbSNP: rs751448793
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668815 SCV000793479 pathogenic DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome type 2 2017-08-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001057555 SCV001222053 pathogenic not provided 2025-01-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg857*) 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 present in population databases (rs751448793, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with Cockayne syndrome or cerebrooculofacioskeletal syndrome (PMID: 18628313, 19894250). ClinVar contains an entry for this variant (Variation ID: 553383). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV004576963 SCV005060940 pathogenic Cockayne syndrome type 2 criteria provided, single submitter clinical testing The stop-gained variant c.2569C>T (p.Arg857Ter) in the ERCC6 gene has been reported in the heterozygous state in individuals affected with Cockayne syndrome and Cerebrooculofacioskeletal syndrome (Laugel et al., 2010; Laugel et al., 2008). This variant is reported with the allele frequency (0.002%) in the gnomAD Exome. It has been submitted to ClinVar as Pathogenic. This variant is predicted to cause a loss of normal protein function through protein truncation. Loss of function variants has been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV004576963 SCV005374442 pathogenic Cockayne syndrome type 2 2024-09-22 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004732993 SCV005360656 pathogenic ERCC6-related disorder 2024-05-16 no assertion criteria provided clinical testing The ERCC6 c.2569C>T variant is predicted to result in premature protein termination (p.Arg857*). This variant was reported in the compound heterozygous state in two individuals with cerebro-oculo-facio-skeletal syndrome (Laugel et al. 2008. PubMed ID: 18628313; Martins et al. 2021. PubMed ID: 34271225). This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD. Nonsense variants in ERCC6 are expected to be pathogenic. This variant is interpreted as pathogenic.

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