ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2389+5G>A

dbSNP: rs879255191
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000237473 SCV004022381 uncertain significance Hypercholesterolemia, familial, 1 2023-03-20 reviewed by expert panel curation The NM_000527.5(LDLR):c.2389+5G>A variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PS4_Supporting, PM2, PP3, and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines ( The supporting evidence is as follows: PS4_Supporting: Variant meets PM2 and is identified in 2 unrelated index cases with DLCN criteria>=6 from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation). So PS4_Supporting is met. PM2: This variant is absent from gnomAD (gnomAD v2.1.1). So PM2 is met. PP3: No REVEL, splicing evaluation needed. Functional data on splicing not available. A) variant located -3 to +6 from canonical donor site MES scores: canonical site variant = 4.93; canonical donor wt = 9.86. Ratio: 4.93/9.86 = 0.5 ---- It is below 0.8 Variant is predicted to alter splicing. So PP3 is met. PP4: Variant meets PM2 and is identified in 2 unrelated index cases who fulfill clinical criteria for FH (see PS4 for details). So PP4 is met.
LDLR-LOVD, British Heart Foundation RCV000237473 SCV000295976 likely benign Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter research
Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation RCV000237473 SCV000540867 pathogenic Hypercholesterolemia, familial, 1 2016-11-05 criteria provided, single submitter clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237473 SCV000606637 benign Hypercholesterolemia, familial, 1 no assertion criteria provided research

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