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]
  • There was no gene found in the curated document received from the VCI/VCEP
  • The variant label for this record ("NC_000019.10:g.11089334A>G") does not appear to be in HGVS format
  • Despite there being a valid 'cspec' property in the messages there's a discrepancy in message contents and CSPEC data: * Message Gene: undefined CSPEC Genes: [ 'LDLR' ] * Message MONDOs: MONDO:0007750 CSPEC MONDO: [ 'MONDO:0007750' ]
  • No CSPEC computed assertion could be determined for this classification!

Variant: NC_000019.10:g.11089334A>G

CA10584692

250928 (ClinVar)

Gene: N/A
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: ab885565-2456-4ec9-accf-2995f2a8eebd
Approved on: 2025-01-31
Published on: 2025-02-03

HGVS expressions

NC_000019.10:g.11089334A>G
CM000681.2:g.11089334A>G
NC_000019.9:g.11200010A>G
CM000681.1:g.11200010A>G
NC_000019.8:g.11061010A>G
NG_009060.1:g.4954A>G
NR_163945.1:n.326T>C
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Uncertain Significance

Met criteria codes 2
PP4 PM2
Not Met criteria codes 3
BS3 PS3 PS4

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.4(LDLR):c.-215A>G 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 31 January 2025. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v4.1.0). PP4: Variant meets PM2 and is identified in at least 1 index case who fulfills Simon Broome criteria for FH from PMID 22881376 (Usifo et al., 2012) after alternative causes of high cholesterol were excluded.
Met criteria codes
PP4
Variant meets PM2 and is identified in at least 1 index case who fulfills SB possible/definite criteria for FH (PMID: 22881376) after alternative causes of high cholesterol were excluded.
PM2
This variant is absent from gnomAD (gnomAD v4.1.0).
Not Met criteria codes
BS3
PS3/BS3: Contradictory functional study evidence is presented in PMID: 25248394. For this reason, neither PS# or BS3 were applied. There is an upcoming luciferase assay study of this variant in CHO cells from Caterina and Rafael that could be used as functional evidence.
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Variant only found in one reported FH case
Curation History
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