ClinVar Miner

Submissions for variant NM_000430.4(PAFAH1B1):c.569-10T>C

dbSNP: rs113994202
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000020304 SCV000194389 pathogenic Lissencephaly due to LIS1 mutation 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000494023 SCV000582158 pathogenic not provided 2023-06-07 criteria provided, single submitter clinical testing Functional studies suggest c.569-10 T>C causes abnormal gene splicing (Philbert et al., 2017); In silico analysis supports a deleterious effect on splicing; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17664403, 11115846, 27891766, 29671837, 36100855)
Eurofins Ntd Llc (ga) RCV000494023 SCV000708127 pathogenic not provided 2017-12-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000623782 SCV000742598 likely pathogenic Inborn genetic diseases 2017-07-25 criteria provided, single submitter clinical testing
Mendelics RCV000020304 SCV001140211 pathogenic Lissencephaly due to LIS1 mutation 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000494023 SCV002160026 pathogenic not provided 2022-08-21 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 21182). For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant results in skipping of exon 7 and introduces a premature termination codon (PMID: 27891766). The resulting mRNA is expected to undergo nonsense-mediated decay. This variant has been observed in individual(s) with lissencephaly (PMID: 11115846, 17664403, 27891766). 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 falls in intron 6 of the PAFAH1B1 gene. It does not directly change the encoded amino acid sequence of the PAFAH1B1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000020304 SCV004046079 pathogenic Lissencephaly due to LIS1 mutation criteria provided, single submitter clinical testing This variant has been previously reported as a de novo change in patients with lissencephaly (PMID: 11115846, 27891766). Functional studies in patient fibroblasts demonstrated that this variant leads to exon skipping (PMID: 27891766). It is absent from the gnomAD population database and thus is presumed to be rare. Analysis of the parental samples was negative for the variant, indicating the variant likely occurred as a de novo event. Based on the available evidence, the c.569-10T>C variant is classified as Pathogenic.
University of Washington Center for Mendelian Genomics, University of Washington RCV001291184 SCV001479607 likely pathogenic Lissencephaly no assertion criteria provided research

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