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.854A>G (p.His285Arg)

CA404080674

450684 (ClinVar)

Gene: LDLR (HGNC:3949)

Condition: hypercholesterolemia, familial (MONDO:0007750)

Inheritance Mode: Semidominant inheritance

UUID: 1e59e697-8a4f-42d0-b9c5-16127233c7b4

Approved on: 2023-03-24

Published on: 2024-12-16

HGVS expressions

NM_000527.5:c.854A>G

NM_000527.5(LDLR):c.854A>G (p.His285Arg)

NC_000019.10:g.11107428A>G

CM000681.2:g.11107428A>G

NC_000019.9:g.11218104A>G

CM000681.1:g.11218104A>G

NC_000019.8:g.11079104A>G

NG_009060.1:g.23048A>G

ENST00000252444.10:c.1112A>G

ENST00000559340.2:c.854A>G

ENST00000560467.2:c.854A>G

ENST00000558518.6:c.854A>G

ENST00000252444.9:c.1108A>G

ENST00000455727.6:c.350A>G

ENST00000535915.5:c.731A>G

ENST00000545707.5:c.473A>G

ENST00000557933.5:c.854A>G

ENST00000558013.5:c.854A>G

ENST00000558518.5:c.854A>G

ENST00000558528.1:n.369A>G

ENST00000560467.1:c.454A>G

NM_000527.4:c.854A>G

NM_001195798.1:c.854A>G

NM_001195799.1:c.731A>G

NM_001195800.1:c.350A>G

NM_001195803.1:c.473A>G

NM_001195798.2:c.854A>G

NM_001195799.2:c.731A>G

NM_001195800.2:c.350A>G

NM_001195803.2:c.473A>G

Uncertain Significance

PM2 BP4

PM3 PM1 PM4 PM5 PM6 BS4 BS3 BS1 BS2 PVS1 PS2 PS4 PS3 PS1 BP7 BP2 BP3 BP1 BA1 PP4 PP1 PP3 PP2

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.854A>G (p.His285Arg) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 24 March 2023. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (v2.1.1). BP4: REVEL = 0.419, splicing evaluation required. A.) Not on limits. B.) Does not create AG. C.) There is an AG nearby. Cryptic scores are negative, so cryptic site is not used - variant is not predicted to alter splicing. BP4 is met.

PM2

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

BP4

REVEL = 0.419, splicing evaluation required. The variant is not predicted to affect splicing.

PM3

Not met.

PM1

Not located in exon 4 or at a cysteine residue.

PM4

Not an in-frame deletion/insertion.

PM5

Not met.

PM6

Not met.

BS4

Not met.

BS3

Not met.

BS1

Not met.

BS2

Not met.

PVS1

Not a null variant.

PS2

Not met.

PS4

Not met.

PS3

Not met.

PS1

Not met.

BP7

Not a synonymous variant.

BP2

Not met.

BP3

Not applicable

BP1

Not applicable

BA1

Not met.

PP4

Not met.

PP1

Not met.

PP3

REVEL = 0.419, splicing evaluation required. Neither scenario A, B or C is met. The variant is not predicted to affect splicing.

PP2

Not applicable

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.