ClinVar Miner

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

dbSNP: rs879255191
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
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 (https://doi.org/10.1016/j.gim.2021.09.012). 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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.