Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523673 | SCV000621139 | pathogenic | not provided | 2017-09-27 | criteria provided, single submitter | clinical testing | The c.2889+1G>A splice site variant in the IQSEC2 gene destroys the canonical splice donor site in intron 9. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that issubject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.2889+1G>A variant is not observed in large population cohorts (Lek et al., 2016). Although this pathogenic variant has not been previously reported to our knowledge, its presence is consistent with the diagnosis of an IQSEC2-related disorder in this individual. |
Invitae | RCV000794238 | SCV000933632 | pathogenic | Intellectual disability, X-linked 1 | 2022-03-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 452339). Disruption of this splice site has been observed in individual(s) with clinical features of IQSEC2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 9 of the IQSEC2 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 IQSEC2 are known to be pathogenic (PMID: 21686261, 26793055, 27665735). |