Evidence Repository - Clinical Genome Resources

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.4G>C (p.Gly2Arg)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA085719

250971 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 610086db-97cc-4269-9e2d-65da8253257c

Approved on: 2022-04-29

Published on: 2025-09-25

HGVS expressions

NM_000527.5:c.4G>C

NM_000527.5(LDLR):c.4G>C (p.Gly2Arg)

NC_000019.10:g.11089552G>C

CM000681.2:g.11089552G>C

NC_000019.9:g.11200228G>C

CM000681.1:g.11200228G>C

NC_000019.8:g.11061228G>C

NG_009060.1:g.5172G>C

ENST00000559340.2:c.4G>C

ENST00000560467.2:c.4G>C

ENST00000558518.6:c.4G>C

ENST00000455727.6:c.4G>C

ENST00000535915.5:c.4G>C

ENST00000545707.5:c.4G>C

ENST00000557933.5:c.4G>C

ENST00000557958.1:n.90G>C

ENST00000558013.5:c.4G>C

ENST00000558518.5:c.4G>C

ENST00000560502.5:n.90G>C

NM_000527.4:c.4G>C

NM_001195798.1:c.4G>C

NM_001195799.1:c.4G>C

NM_001195800.1:c.4G>C

NM_001195803.1:c.4G>C

NM_001195798.2:c.4G>C

NM_001195799.2:c.4G>C

NM_001195800.2:c.4G>C

NM_001195803.2:c.4G>C

NR_163945.1:n.108C>G

Uncertain Significance

PP4 PM2

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.4G>C (p.Gly2Arg) variant is classified as uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2 and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2 - PopMax MAF = 0.00016 (0.016%) in African exomes (gnomAD v2.1.1). PP4 - Variant meets PM2 and is identified in one index cases who fulfills SB criteria for FH (1 case from CGMC, UFGOD (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière)).

PP4

PM2 is met and is identified in one index cases who fulfil SB criteria for FH (Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière))

PM2

PopMax MAF = 0.0001629 (0.016%) in African/African American exomes (gnomAD v2.1.1)

Curation History

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