Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000779279 | SCV000915858 | uncertain significance | Xeroderma pigmentosum group B | 2017-04-28 | criteria provided, single submitter | clinical testing | The ERCC3 c.1757_1758delAG (p.Gln586ArgfsTer17) variant results in a frameshift and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found reporting the p.Gln586ArgfsTer17 variant in association with xeroderma pigmentosum. The variant was reported in one study in which it was found in a heterozygous state in a patient with thyroid cancer (Guan et al. 2015). This variant is reported at a frequency of 0.00012 in the East Asian population from the Exome Aggregation Consortium, but this frequency is based on one allele in a region of good sequence coverage. The variant is thus presumed to be rare. The evidence for this variant is limited. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of uncertain significance but suspicious for pathogenicity for xeroderma pigmentosum. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV001856170 | SCV002226904 | pathogenic | not provided | 2023-05-10 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs774261851, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Gln586Argfs*17) in the ERCC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC3 are known to be pathogenic (PMID: 16947863). This variant has not been reported in the literature in individuals affected with ERCC3-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 632330). |