ClinVar Miner

Submissions for variant NM_001111125.3(IQSEC2):c.2889+1G>A (rs1556861311)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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 likely pathogenic Mental retardation, X-linked 1 2018-07-30 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the IQSEC2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with  microcephaly, DD, seizures (Invitae). ClinVar contains an entry for this variant (Variation ID: 452339). Donor and acceptor splice site variants 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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