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.82G>A (p.Glu28Lys)

CA041712

430745 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: e7226ef0-9ba0-4b96-8400-ce6cceb7d303

HGVS expressions

NM_000527.5:c.82G>A

NM_000527.5(LDLR):c.82G>A (p.Glu28Lys)

NC_000019.10:g.11100237G>A

CM000681.2:g.11100237G>A

NC_000019.9:g.11210913G>A

CM000681.1:g.11210913G>A

NC_000019.8:g.11071913G>A

NG_009060.1:g.15857G>A

ENST00000558518.6:c.82G>A

ENST00000252444.9:n.336G>A

ENST00000455727.6:c.82G>A

ENST00000535915.5:c.82G>A

ENST00000545707.5:c.82G>A

ENST00000557933.5:c.82G>A

ENST00000557958.1:n.168G>A

ENST00000558013.5:c.82G>A

ENST00000558518.5:c.82G>A

ENST00000560502.5:n.168G>A

NM_000527.4:c.82G>A

NM_001195798.1:c.82G>A

NM_001195799.1:c.82G>A

NM_001195800.1:c.82G>A

NM_001195803.1:c.82G>A

NM_001195798.2:c.82G>A

NM_001195799.2:c.82G>A

NM_001195800.2:c.82G>A

NM_001195803.2:c.82G>A

Uncertain Significance

BP4

PS4 PP4 PM2 PM5 PM1

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.82G>A (p.Glu28Lys) variant is classified as a variant of uncertain significance for Familial Hypercholesterolemia by applying evidence code 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_Met : REVEL = 0.306. It is below 0.50. splicing evaluation is required. A) not on limits B) does not create AG C) there is a AG nearby The variant does not alter splicing

BP4

REVEL = 0.306. It is below 0.50. splicing evaluation is required. A) not on limits B) does not create AG C) there is a AG nearby The variant does not alter splicing

PS4

variant is identified in 4 probands with relevant phenotypes. However, the variant does not met PM2 code

PP4

variant was found in 4 unrelated patients as having FH but does not Met PM2 code

PM2

MAF=0.00214 in Latino exomes/genomes (gnomAD v.2.1.1)

PM5

There is 1 missense variant in the same codon, classified as pathogenic but not by these guidelines.

PM1

variant is not located in a mutational hot spot and/or critical and well-established functional domain (exon 2).

Approved on: 2022-10-28

Published on: 2022-12-24

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