ClinVar Miner

Submissions for variant NM_001111125.3(IQSEC2):c.2911C>T (p.Arg971Ter)

dbSNP: rs1131691887
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494394 SCV000583058 pathogenic not provided 2022-12-04 criteria provided, single submitter clinical testing 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: 31439632, 32741404, 30666632, 33504798, 33368194)
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV000494394 SCV001334366 likely pathogenic not provided 2019-05-16 criteria provided, single submitter clinical testing
Invitae RCV001385379 SCV001585214 pathogenic Intellectual disability, X-linked 1 2024-01-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg971*) in the IQSEC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IQSEC2 are known to be pathogenic (PMID: 21686261, 26793055, 27665735). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of IQSEC2-related conditions (PMID: 30666632). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 430286). For these reasons, this variant has been classified as Pathogenic.
3billion RCV001385379 SCV003841658 pathogenic Intellectual disability, X-linked 1 2023-02-23 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000430286 / PMID: 30666632). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

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