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.2389+41C>A

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA040197

252310 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 750f946d-144d-4cee-9fb3-b3faa27f5791

Approved on: 2025-03-24

Published on: 2025-03-24

HGVS expressions

NM_000527.5:c.2389+41C>A

NM_000527.5(LDLR):c.2389+41C>A

NC_000019.10:g.11128126C>A

CM000681.2:g.11128126C>A

NC_000019.9:g.11238802C>A

CM000681.1:g.11238802C>A

NC_000019.8:g.11099802C>A

NG_009060.1:g.43746C>A

ENST00000252444.10:c.2647+41C>A

ENST00000559340.2:c.*458+41C>A

ENST00000560467.2:c.2269+41C>A

ENST00000558518.6:c.2389+41C>A

ENST00000252444.9:c.2643+41C>A

ENST00000455727.6:c.1885+41C>A

ENST00000535915.5:c.2266+41C>A

ENST00000545707.5:c.1855+41C>A

ENST00000557933.5:c.2389+41C>A

ENST00000558013.5:c.2389+41C>A

ENST00000558518.5:c.2389+41C>A

ENST00000560628.1:n.108+472C>A

NM_000527.4:c.2389+41C>A

NM_001195798.1:c.2389+41C>A

NM_001195799.1:c.2266+41C>A

NM_001195800.1:c.1885+41C>A

NM_001195803.1:c.1855+41C>A

NM_001195798.2:c.2389+41C>A

NM_001195799.2:c.2266+41C>A

NM_001195800.2:c.1885+41C>A

NM_001195803.2:c.1855+41C>A

Benign

BA1 BP4

PP4 PP1 PP3 PM3 PM2 BS1 BP2 PS4

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.2389+41C>A variant is classified as Benign for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes BA1 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 24 March 2025. The supporting evidence is as follows: BA1: FAF = 0.01376 (1.376%) in African/African American exomes (gnomAD v4.1.0). BP4: No REVEL, splicing evaluation required. Functional data on splicing not available. A) not on limits. B) Does not create a GT. C) No nearby GT. Variant is not predicted to alter splicing.

BA1

FAF = 0.01376 (1.376%) in African/African American exomes (gnomAD v4.1.0).

BP4

No REVEL, splicing evaluation required. Functional data on splicing not available. A) not on limits. B) Does not create a GT. C) No nearby GT. Variant is not predicted to alter splicing.

PP4

Variant does not meet PM2

PP1

Variant segregates in only 1 informative meiosis

PP3

Variant is not a missense variant and does not meet PM2

PM3

Variant does not meet PM2

PM2

PopMax MAF = 0.01527 (1.527%) in African/African American exomes+genomes (gnomAD v4.1.0).

BS1

FAF = 0.01376 (1.376%) in African/African American exomes (gnomAD v4.1.0).

BP2

Cis/trans status unknown

PS4

Variant does not meet PM2 despite being identified in 19 unrelated FH cases

Curation History

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