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>C (p.Asp589His)

CA023571

183125 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: d21e9a49-db05-4d2d-92be-523fc05c0d80

HGVS expressions

NM_000527.5:c.1765G>C

NM_000527.5(LDLR):c.1765G>C (p.Asp589His)

NC_000019.10:g.11116918G>C

CM000681.2:g.11116918G>C

NC_000019.9:g.11227594G>C

CM000681.1:g.11227594G>C

NC_000019.8:g.11088594G>C

NG_009060.1:g.32538G>C

ENST00000558518.6:c.1765G>C

ENST00000252444.9:n.2019G>C

ENST00000455727.6:c.1261G>C

ENST00000535915.5:c.1642G>C

ENST00000545707.5:c.1384G>C

ENST00000557933.5:c.1765G>C

ENST00000558013.5:c.1765G>C

ENST00000558518.5:c.1765G>C

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

NM_000527.4:c.1765G>C

NM_001195798.1:c.1765G>C

NM_001195799.1:c.1642G>C

NM_001195800.1:c.1261G>C

NM_001195803.1:c.1384G>C

NM_001195798.2:c.1765G>C

NM_001195799.2:c.1642G>C

NM_001195800.2:c.1261G>C

NM_001195803.2:c.1384G>C

Uncertain Significance

PM2 BP4

PP3 BS3 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>C (p.Asp589His) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2 and 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: PM2 - PopMax MAF = 0.000008790 (0.0009%) in Non-Finnish European exomes+genomes (gnomAD v2.1.1) BP4 - REVEL = 0.424. 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

PM2

PopMax MAF = 0.000008790 (0.0009%) in Non-Finnish European exomes+genomes (gnomAD v2.1.1)

BP4

REVEL = 0.424. 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

PP3

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

BS3

assay from PMID: 2567241 not appropriate

PM5

two other variants at the same codon but both classified as VUS

Approved on: 2022-08-29

Published on: 2022-12-23

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