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: 3
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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
Invitae RCV001057555 SCV001222053 pathogenic not provided 2023-12-03 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.

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