Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: LDLR vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000527.5(LDLR):c.1504G>T (p.Asp502Tyr)

CA10585485

251877 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 158831f7-f155-4b50-97d9-9f1c74307cf3
Approved on: 2025-02-28
Published on: 2025-04-08

HGVS expressions

NM_000527.5:c.1504G>T
NM_000527.5(LDLR):c.1504G>T (p.Asp502Tyr)
NC_000019.10:g.11113680G>T
CM000681.2:g.11113680G>T
NC_000019.9:g.11224356G>T
CM000681.1:g.11224356G>T
NC_000019.8:g.11085356G>T
NG_009060.1:g.29300G>T
ENST00000252444.10:c.1762G>T
ENST00000559340.2:c.1504G>T
ENST00000560467.2:c.1384G>T
ENST00000558518.6:c.1504G>T
ENST00000252444.9:c.1758G>T
ENST00000455727.6:c.1000G>T
ENST00000535915.5:c.1381G>T
ENST00000545707.5:c.1123G>T
ENST00000557933.5:c.1504G>T
ENST00000558013.5:c.1504G>T
ENST00000558518.5:c.1504G>T
ENST00000559340.1:c.225G>T
NM_000527.4:c.1504G>T
NM_001195798.1:c.1504G>T
NM_001195799.1:c.1381G>T
NM_001195800.1:c.1000G>T
NM_001195803.1:c.1123G>T
NM_001195798.2:c.1504G>T
NM_001195799.2:c.1381G>T
NM_001195800.2:c.1000G>T
NM_001195803.2:c.1123G>T
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Uncertain Significance

Met criteria codes 2
PP4 PM2
Not Met criteria codes 1
PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Familial Hypercholesterolemia Expert Panel Specifications to the ACMG/AMP Variant Classification Guidelines Version 1.2

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.1504G>T p.(Asp502Tyr) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2 and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on February 28, 2025. PM2: This variant is absent from gnomAD (gnomAD v4.1.0). PP4: Variant meets PM2 and is identified in one FH case from The Netherlands fulfilling internationally accepted criteria, after alternative causes of high cholesterol were excluded, in PMID 11810272 (Fouchier et al., 2001).
Met criteria codes
PP4
PP4: Variant meets PM2 and is identified in one FH case from The Netherlands fulfilling internationally accepted criteria (Defesche 2000), after alternative causes of high cholesterol were excluded (PMID: 11810272).
PM2
This variant is absent from gnomAD (gnomAD v4.1.0).
Not Met criteria codes
PP3
REVEL = 0.699 creates GT: >var de novo TGCGTATAC MAXENT: -11.90 >canonical TGGgtgcgt MAXENT: 5.46 negative 1 AG nearby >wt TCTCTGTTGCGGATACCAAGGGC MAXENT: 1.62 >var TCTCTGTTGCGTATACCAAGGGC MAXENT: 4.50 >canonical cttctctcctcctgcctcagCAC MAXENT: 6.76 Ratio variant cryptic/wt cryptic: 4.50/1.62 = 2.78 --- it is above 1.1 Ratio variant cryptic/canonical acceptor/donor: 4.50/6.76 = 0.666 --- it is NOT above 0.9"
Curation History
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