Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479437 | SCV000569795 | likely pathogenic | not provided | 2016-03-28 | criteria provided, single submitter | clinical testing | The c.1666-2A>T variant in the ERCC2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice acceptor site in intron 17. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1666-2A>T variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1666-2A>T as a likely pathogenic variant. |
| Labcorp Genetics |
RCV000479437 | SCV003484652 | pathogenic | not provided | 2024-05-22 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 17 of the ERCC2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ERCC2 are known to be pathogenic (PMID: 9238033, 11335038, 19085937, 19934020). This variant is present in population databases (rs199658345, gnomAD 0.002%). Disruption of this splice site has been observed in individual(s) with clinical features of trichothiodystrophy (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 420816). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003470562 | SCV004194648 | likely pathogenic | Cerebrooculofacioskeletal syndrome 2 | 2023-08-19 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005018808 | SCV005648395 | likely pathogenic | Cerebrooculofacioskeletal syndrome 2; Xeroderma pigmentosum, group D; Trichothiodystrophy 1, photosensitive | 2024-02-09 | criteria provided, single submitter | clinical testing |