Submissions for variant NM_000124.4(ERCC6):c.4063-1G>C

gnomAD frequency: 0.00002  dbSNP: rs766980240

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000664549	SCV000788531	likely pathogenic	DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome type 2	2017-07-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000994388	SCV001147883	likely pathogenic	not provided	2019-11-01	criteria provided, single submitter	clinical testing
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences	RCV001528150	SCV001451943	pathogenic	Cockayne syndrome type 2		criteria provided, single submitter	research
Labcorp Genetics (formerly Invitae), Labcorp	RCV000994388	SCV001590180	pathogenic	not provided	2023-05-13	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 20 of the ERCC6 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 549960). Disruption of this splice site has been observed in individuals with Cockayne syndrome (PMID: 19894250, 29572252). This variant is present in population databases (rs766980240, gnomAD 0.02%).
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV001528150	SCV002059952	pathogenic	Cockayne syndrome type 2		criteria provided, single submitter	clinical testing
Department of Biochemistry, Faculty of Medicine, University of Khartoum	RCV001528150	SCV002573715	pathogenic	Cockayne syndrome type 2		criteria provided, single submitter	research
Neuberg Centre For Genomic Medicine, NCGM	RCV001528150	SCV004101488	uncertain significance	Cockayne syndrome type 2		criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in the last intron (intron 20) of the ERCC6 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant has been observed in individual(s) with Cockayne syndrome (Calmels N et al, Laugel V et al). This variant has been reported to the ClinVar database as Pathogenic/ Likely pathogenic. The variant is reported in gnomAD with the allele frequency of 002006% and is novel (not in any individuals) in 1000 Genomes. The nucleotide change in ERCC6 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as pathogenic.
Revvity Omics, Revvity	RCV000994388	SCV004235173	pathogenic	not provided	2023-03-06	criteria provided, single submitter	clinical testing