ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2141-218G>A

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Total submissions: 1
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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 RCV004702889 SCV005203693 likely pathogenic Familial hypercholesterolemia 2024-07-03 criteria provided, single submitter clinical testing Variant summary: LDLR c.2141-218G>A is located at a position not widely known to affect splicing. Two computation tools predict no significant impact on normal splicing, while two predict the variant creates or strengthens a cryptic 5' splicing donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing, resulting in the insertion of intronic material that includes a premature stop codon (Reeskamp_2021). The variant was absent in 31172 control chromosomes (gnomAD). c.2141-218G>A has been reported in the literature in individuals affected with Familial Hypercholesterolemia with evidence of cosegregation with disease (Reeskamp_2021). The following publication has been ascertained in the context of this evaluation (PMID: 33601267). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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