Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001851900 | SCV002183074 | pathogenic | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 16585). This premature translational stop signal has been observed in individual(s) with ERCC3-related conditions (PMID: 16947863, 26884178). This variant is present in population databases (rs121913047, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Arg425*) 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). |
| Gene |
RCV001851900 | SCV002513147 | pathogenic | not provided | 2023-04-11 | criteria provided, single submitter | clinical testing | Reported in trans with a second ERCC3 variant in two sisters with features of xeroderma pigmentosa (Oh et al., 2006); Published functions studies demonstrate a damaging effect resulting in defective DNA repair activity (Oh et al., 2006); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 20947453, 26884178, 28588253, 29376097, 27004399, 19199647, 16947863, 26689913, 29625052) |
| Ambry Genetics | RCV002513092 | SCV003631936 | pathogenic | Inborn genetic diseases | 2022-07-21 | criteria provided, single submitter | clinical testing | The c.1273C>T (p.R425*) alteration, located in exon 8 (coding exon 8) of the ERCC3 gene, consists of a C to T substitution at nucleotide position 1273. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 425. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of <0.01% (2/251402) total alleles studied. The highest observed frequency was <0.01% (2/113682) of European (non-Finnish) alleles. This alteration has been reported along with a second ERCC3 alteration in patients with features of ERCC3-related spectrum disorders (Garcia-Moreno, 2018; Oh, 2006). Functional studies show that this alteration leads to greatly reduced activity compared to wild type (Oh, 2006). Based on the available evidence, this alteration is classified as pathogenic. |
| OMIM | RCV000018053 | SCV000038332 | pathogenic | Xeroderma pigmentosum group B | 2006-11-01 | no assertion criteria provided | literature only |