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

gnomAD frequency: 0.00001  dbSNP: rs786205171

Total submissions: 7

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
Labcorp Genetics (formerly Invitae), Labcorp	RCV000224382	SCV001397216	pathogenic	not provided	2024-08-21	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)
Fulgent Genetics, Fulgent Genetics	RCV005049452	SCV005680155	pathogenic	DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome type 2; UV-sensitive syndrome 1; Age related macular degeneration 5; Premature ovarian failure 11; Lung cancer	2024-05-07	criteria provided, single submitter	clinical testing