Submissions for variant NM_000124.4(ERCC6):c.4177del (p.Lys1392_Met1393insTer)

dbSNP: rs1850531575

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV001089544	SCV001244758	likely pathogenic	Cockayne syndrome type 2	2018-05-29	criteria provided, single submitter	clinical testing	A homozygous nonsense variant, NM_000124.3(ERCC6):c.4177delA, has been identified in exon 21 of 21 of the ERCC6 gene. The variant is predicted to result in a premature stop codon at position 1393 of the protein (NP_000115.1(ERCC6):p.(Met1393*)). This variant is predicted to result in a truncated protein, with no known functional domains affected. Multiple pathogenic truncating variants have previously been reported upstream of this variant (ClinVar), resulting in loss of protein function through nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. One pathogenic truncating variant downstream of this variant has been reported (Personal communication). Following multidisciplinary clinical review of this case, this variant was determined to be highly concordant with the phenotypic presentaion of the patient. Based on the information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC.