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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000527.5(LDLR):c.1765G>A (p.Asp589Asn)

CA036508

252022 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: fd0cb6c9-7f1e-4644-9c34-95083a79a553

HGVS expressions

NM_000527.5:c.1765G>A

NM_000527.5(LDLR):c.1765G>A (p.Asp589Asn)

NC_000019.10:g.11116918G>A

CM000681.2:g.11116918G>A

NC_000019.9:g.11227594G>A

CM000681.1:g.11227594G>A

NC_000019.8:g.11088594G>A

NG_009060.1:g.32538G>A

ENST00000558518.6:c.1765G>A

ENST00000252444.9:n.2019G>A

ENST00000455727.6:c.1261G>A

ENST00000535915.5:c.1642G>A

ENST00000545707.5:c.1384G>A

ENST00000557933.5:c.1765G>A

ENST00000558013.5:c.1765G>A

ENST00000558518.5:c.1765G>A

ENST00000559340.1:n.426+706G>A

NM_000527.4:c.1765G>A

NM_001195798.1:c.1765G>A

NM_001195799.1:c.1642G>A

NM_001195800.1:c.1261G>A

NM_001195803.1:c.1384G>A

NM_001195798.2:c.1765G>A

NM_001195799.2:c.1642G>A

NM_001195800.2:c.1261G>A

NM_001195803.2:c.1384G>A

Uncertain Significance

BP4

BP5 PS4 PM2 PM5

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5(LDLR):c.1765G>A (p.Asp589Asn) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes BP4 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: BP4 - REVEL = 0.325. It is below 0.5, splicing evaluation needed. Functional data on splicing not available. A) variant not on limits. B) does not create AG or GT Variant is not predicted to alter splicing

BP4

BP4 - REVEL = 0.325. It is below 0.5, splicing evaluation needed. Functional data on splicing not available. A) variant not on limits. B) does not create AG or GT Variant is not predicted to alter splicing

BP5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS4

MAF = 0.105% in East Asians

PM2

PM2 - PopMax MAF = 0.001053 (0.11%) in East-Asian European exomes/genomes (gnomAD v2.1.1).

PM5

2 other variants in the same codon but both are classified as VUS per ClinGen LDLR VCEP guidelines

Approved on: 2022-08-29

Published on: 2022-12-23

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