Evidence Repository - GenboreeKB

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000527.5(LDLR):c.2547+5G>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10585882

252354 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: c11995af-6401-43d3-aef9-3a20a29d544c

Approved on: 2023-04-26

Published on: 2025-02-13

HGVS expressions

NM_000527.5:c.2547+5G>C

NM_000527.5(LDLR):c.2547+5G>C

NC_000019.10:g.11129675G>C

CM000681.2:g.11129675G>C

NC_000019.9:g.11240351G>C

CM000681.1:g.11240351G>C

NC_000019.8:g.11101351G>C

NG_009060.1:g.45295G>C

ENST00000252444.10:c.2805+5G>C

ENST00000559340.2:c.*616+5G>C

ENST00000560467.2:c.2427+5G>C

ENST00000558518.6:c.2547+5G>C

ENST00000252444.9:c.2801+5G>C

ENST00000455727.6:c.2043+5G>C

ENST00000535915.5:c.2424+5G>C

ENST00000545707.5:c.2013+5G>C

ENST00000557933.5:c.2609+5G>C

ENST00000558013.5:c.2547+5G>C

ENST00000558518.5:c.2547+5G>C

ENST00000560628.1:n.108+2021G>C

NM_000527.4:c.2547+5G>C

NM_001195798.1:c.2547+5G>C

NM_001195799.1:c.2424+5G>C

NM_001195800.1:c.2043+5G>C

NM_001195803.1:c.2013+5G>C

NM_001195798.2:c.2547+5G>C

NM_001195799.2:c.2424+5G>C

NM_001195800.2:c.2043+5G>C

NM_001195803.2:c.2013+5G>C

Uncertain Significance

PM2 PP3 PP4

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

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.2547+5G>C variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PP3 and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 26 April 2023. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v2.1.1). PP3: No REVEL, splicing evaluation required. Functional data on splicing not available. A) variant located at -3 to +6 from canonical donor splice site. MES scores: canonical site variant = 3.74; canonical site wt = 11.11. Ratio variant/wt canonical donor: 3.74/11.11 = 0.34 --- it is below 0.8 Variant is predicted to alter splicing. PP4: Variant meet PM2 and is identified in 1 index case who fulfils Simon Broome criteria for FH (PMID 20809525, Marduel et al. 2010) after alternative causes of high cholesterol are excluded.

PM2

This variant is absent from gnomAD (gnomAD v2.1.1).

PP3

PP3 - No REVEL, splicing evaluation required. Functional data on splicing not available. A) variant located at -3 to +6 from canonical donor splice site. MES scores: canonical site variant = 3.74; canonical site wt = 11.11. Ratio variant/wt canonical donor: 3.74/11.11 = 0.34 --- it is below 0.8 Variant is predicted to alter splicing.

PP4

Variant meet PM2 and is identified in 1 index case who fulfils SB criteria for FH PMID: 20809525 after alternative causes of high cholesterol are excluded.

Curation History

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