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]
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  • There was no gene found in the curated document received from the VCI/VCEP
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  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000527.4(LDLR):c.-187_-185del

CA645509248

438314 (ClinVar)

Gene: N/A
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 86c86059-5846-4a77-ad34-089d165c8f16
Approved on: 2023-04-28
Published on: 2024-10-02

HGVS expressions

NM_000527.4(LDLR):c.-187_-185del
NC_000019.10:g.11089362_11089364del
CM000681.2:g.11089362_11089364del
NC_000019.9:g.11200038_11200040del
CM000681.1:g.11200038_11200040del
NC_000019.8:g.11061038_11061040del
NG_009060.1:g.4982_4984del
NR_163945.1:n.302_304del

Uncertain Significance

Met criteria codes 2
PS3_Supporting PM2
Not Met criteria codes 2
PP4 BP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5 (LDLR):c.-187_185del variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2 and PS3_Supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 28 April 2023. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD version 2.1.1). PS3_Supporting: Level 3 experiment, heterologous cells (HepG2) were used for luciferase assays, 8% reporter gene expression observed, PMID 9610768 (Peeters et al., 1998).
Met criteria codes
PS3_Supporting
Level 3 experiment, heterologous cells (HepG2) were used for luciferase assays, 8% reporter gene expression observed, published by Peeters et al., 1998, PMID 9610768.
PM2
This variant is absent from gnomAD (gnomAD version 2.1.1).
Not Met criteria codes
PP4
Variant meets PM2 and is identified in 1 index case who fulfil DLCN definite FH criteria with heterozygous phenotype, reported by van Wingerden, 1981, Department of Medicine, Groothoek Hospital, Lebowa, PMID 7280910. However, this patient with heterozygous FH phenotype also carries pathogenic LDLR: c.172delG (p.Glu58fs) which alone could explain the phenotype, reported by Peeters et al, 1998, PMID 9610768.
BP2
Variant identified in an index case with heterozygous FH phenotype (LDL-C 7.69 mmol/l) and NM_000527.5 (LDLR):c.172delG (p.Glu58fs), classified as Pathogenic by these guidelines. However two variants were not confirmed in trans, reported by Peeters et al, 1998, PMID 9610768.
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