Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000605921 | SCV000731381 | likely pathogenic | Xeroderma pigmentosum | 2017-03-04 | criteria provided, single submitter | clinical testing | The p.Lys392X (NM_000123.3 c.1173dup) variant in ERCC5 has not been previously r eported in individuals with xeroderma pigmentosum and was absent from large popu lation studies. This variant is predicted to cause a frameshift, which alters th e protein?s amino acid sequence and leads to a premature termination codon at po sition 392. This alteration is then predicted to lead to a truncated or absent p rotein. Biallelic loss of function in ERCC5 has been associated with xeroderma p igmentosum. In summary, although additional studies are required to fully establ ish a null effect on the protein, the p.Lys392X variant in ERCC5 is likely patho genic for xeroderma pigmentosum in an autosomal recessive manner based upon its predicted functional impact. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000605921 | SCV005040090 | pathogenic | Xeroderma pigmentosum | 2024-03-07 | criteria provided, single submitter | clinical testing | Variant summary: ERCC5 c.1173dupT (p.Lys392X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 251034 control chromosomes. c.1173dupT has been reported in the literature at a compound heterozygous state with a second pathogenic variant in at-least one individual affected with Xeroderma Pigmentosum (example, Zhang_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 27982466). ClinVar contains an entry for this variant (Variation ID: 517221). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV005004270 | SCV005632783 | pathogenic | Xeroderma pigmentosum, group G; Cerebrooculofacioskeletal syndrome 3 | 2024-03-08 | criteria provided, single submitter | clinical testing |