ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.954_958+7del

dbSNP: rs2132025021
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001358712 SCV001554540 likely pathogenic Familial dysautonomia 2021-03-29 criteria provided, single submitter clinical testing Variant summary: IKBKAP (also known as ELP1) c.954_958+7del12 spans the canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251456 control chromosomes. To our knowledge, no occurrence of c.954_958+7del12 in individuals affected with Familial Dysautonomia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV001871954 SCV002317696 likely pathogenic not provided 2020-12-02 criteria provided, single submitter clinical testing 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. This variant has not been reported in the literature in individuals with ELP1-related conditions. This variant is not present in population databases (ExAC no frequency). This variant results in the deletion of part of exon 10 (c.954_958+7del) of the ELP1 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 ELP1 are known to be pathogenic (PMID: 18303054, 24173031).

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