ClinVar

Description

Variant summary: ERCC6 c.3952_3953delAG (p.Arg1318GlyfsX12) 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 in ClinVar database. The variant allele was found at a frequency of 2e-05 in 251212 control chromosomes (gnomAD). c.3952_3953delAG has been reported in the literature in two individuals affected with Cockayne Syndrome (Calmels_2018), one individual with clinical diagnosis and family history of hearing loss, loss of ambulation, hypotonia, cerebellar ataxia and sensory neuropathy (Monies_2019), one individual affected with acute lymphoblastic leukemia (Qin_2020) and one individual affected with malignant peritoneal mesothelioma (Hung_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic (n=2) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic.