Submissions for variant NM_000124.4(ERCC6):c.2839C>T (p.Arg947Ter)

gnomAD frequency: 0.00004  dbSNP: rs906755254

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000592438	SCV000708797	pathogenic	not provided	2017-05-30	criteria provided, single submitter	clinical testing
Counsyl	RCV000674384	SCV000799709	likely pathogenic	DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome type 2	2018-05-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000592438	SCV001582266	pathogenic	not provided	2023-10-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg947*) 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 (no rsID available, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Cockayne syndrome (PMID: 29572252). ClinVar contains an entry for this variant (Variation ID: 502165). For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM	RCV004821283	SCV005442646	pathogenic	Cockayne syndrome type 2	2023-06-22	criteria provided, single submitter	clinical testing	The observed stop gained c.2839C>Tp.Arg947Ter variant in ERCC6 gene has been reported previously in homozygous and compound heterozygous states in individuals affected with Cockayne syndrome Calmels N, et al., 2018; Duong NT, et al., 2022. The c.2839C>T variant is present with 0.0004% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Likely Pathogenic / Pathogenic. The nucleotide change c.2839C>T in ERCC6 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This sequence change creates a premature translational stop signal p.Arg947Ter in the ERCC6 gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing Calmels N, et al., 2018. For these reasons, this variant has been classified as Pathogenic. In absence of another reportable variant in ERCC6 gene, the molecular diagnosis is not confirmed.
Fulgent Genetics, Fulgent Genetics	RCV005044894	SCV005679819	likely 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	2024-06-06	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000592438	SCV001952558	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000592438	SCV001964865	pathogenic	not provided		no assertion criteria provided	clinical testing