Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000665546 | SCV000789688 | likely pathogenic | DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome type 2 | 2017-02-09 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000809201 | SCV000949344 | pathogenic | not provided | 2021-08-31 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV001449817 | SCV001653117 | pathogenic | Cockayne syndrome type 2 | 2021-02-22 | criteria provided, single submitter | clinical testing | The p.Lys337X variant in ERCC6 has been reported in a compound heterozygous state in an individual with Cockayne syndrome, who carried a second pathogenic variant in ERCC6 (Troelstra 1992 PMID: 1339317, Schmickel 1977 PMID: 887325). It has also been identified in 1/113716 European chromosomes by gnomAD (http://gnomad.broadinstitute.org) and reported in ClinVar (Variation ID 550722). This nonsense variant leads to a premature termination codon at position 337, which is predicted to lead to a truncated or absent protein. Loss of function of the ERCC6 gene is an established disease mechanism in autosomal recessive Cockayne syndrome. An animal model in ERCC6 has shown that a similar variant causes some features of Cockayne Syndrome including photosensitivity, but only mild deficits in growth and neurologic function (van Der Horst 1997 PMID: 9150142). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Cockayne syndrome. ACMG/AMP criteria applied: PVS1, PM2_Suporting, PM3, PS3_Moderate. |