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Variant: NM_000527.5(LDLR):c.1402G>A (p.Val468Ile)

CA023485

183115 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
UUID: 5d3b20b1-f41e-4293-8e34-7f435c358ec8
Approved on: 2022-08-29
Published on: 2022-12-23

HGVS expressions

NM_000527.5:c.1402G>A
NM_000527.5(LDLR):c.1402G>A (p.Val468Ile)
NC_000019.10:g.11113578G>A
CM000681.2:g.11113578G>A
NC_000019.9:g.11224254G>A
CM000681.1:g.11224254G>A
NC_000019.8:g.11085254G>A
NG_009060.1:g.29198G>A
ENST00000558518.6:c.1402G>A
ENST00000252444.9:n.1656G>A
ENST00000455727.6:c.898G>A
ENST00000535915.5:c.1279G>A
ENST00000545707.5:c.1021G>A
ENST00000557933.5:c.1402G>A
ENST00000558013.5:c.1402G>A
ENST00000558518.5:c.1402G>A
ENST00000559340.1:n.123G>A
ENST00000560467.1:n.882G>A
NM_000527.4:c.1402G>A
NM_001195798.1:c.1402G>A
NM_001195799.1:c.1279G>A
NM_001195800.1:c.898G>A
NM_001195803.1:c.1021G>A
NM_001195798.2:c.1402G>A
NM_001195799.2:c.1279G>A
NM_001195800.2:c.898G>A
NM_001195803.2:c.1021G>A
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Uncertain Significance

Met criteria codes 3
BP4 PP4 PM2
Not Met criteria codes 1
BS3

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.1402G>A (p.Val468Ile) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, PP4, BP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PM2 - PopMax MAF = 0.0001146 (0.012%) in non-Finnish European exomes/genomes (gnomAD v2.1.1). PP4 - Variant meets PM2 and is identified in at least 1 index case (Robarts Research Institute - 1 index case w/ DLCN>=6), after alternative causes of high cholesterol have been excluded. BP4 - REVEL = 0.239. It is below 0.50. splicing evaluation required. Functional data not available A) not on limits B) does not create AG Variant is not predicted to alter splicing
Met criteria codes
BP4
BP4 - REVEL = 0.239. It is below 0.50. splicing evaluation required. Functional data not available A) not on limits B) does not create AG Variant is not predicted to alter splicing
PP4
PP4 - Variant meets PM2 and is identified in at least 1 index case (Robarts Research Institute - 1 index case w/ DLCN>=6), after alternative causes of high cholesterol have been excluded.
PM2
PM2 - PopMax MAF = 0.0001146 (0.012%) in non-Finnish European exomes/genomes (gnomAD v2.1.1).
Not Met criteria codes
BS3
Does not apply per discussion with VCEP
Curation History
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