Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV001354934 | SCV001549663 | likely pathogenic | not provided | no assertion criteria provided | clinical testing | The ERCC5 p.R366* variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs966111552) and in control databases in 5 of 282436 chromosomes at a frequency of 0.00001770 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. The c.1096C>T variant leads to a premature stop codon at position 366 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the ERCC5 gene are an established mechanism of disease in autosomal recessive xeroderma pigmentosum and is the type of variant expected to cause the disorder when found in the heterozygous or compound heterozygous state. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic. |