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.859G>A (p.Gly287Ser)

CA023782

161280 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: d76af77c-2e61-4be5-9121-173c148bc3db

HGVS expressions

NM_000527.5:c.859G>A

NM_000527.5(LDLR):c.859G>A (p.Gly287Ser)

NC_000019.10:g.11107433G>A

CM000681.2:g.11107433G>A

NC_000019.9:g.11218109G>A

CM000681.1:g.11218109G>A

NC_000019.8:g.11079109G>A

NG_009060.1:g.23053G>A

ENST00000558518.6:c.859G>A

ENST00000252444.9:n.1113G>A

ENST00000455727.6:c.355G>A

ENST00000535915.5:c.736G>A

ENST00000545707.5:c.478G>A

ENST00000557933.5:c.859G>A

ENST00000558013.5:c.859G>A

ENST00000558518.5:c.859G>A

ENST00000558528.1:n.374G>A

ENST00000560467.1:n.459G>A

NM_000527.4:c.859G>A

NM_001195798.1:c.859G>A

NM_001195799.1:c.736G>A

NM_001195800.1:c.355G>A

NM_001195803.1:c.478G>A

NM_001195798.2:c.859G>A

NM_001195799.2:c.736G>A

NM_001195800.2:c.355G>A

NM_001195803.2:c.478G>A

Uncertain Significance

PP3 PM2 PM5

PS3

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5 (LDLR):c.859G>A (p.Gly287Ser) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, PP3, PM5) 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: PopMaxMAF=0.00003 in South Asian population in gnomAD (gnomAD v2.1.1). PP3: REVEL=0.902. PM5: One other variant at same codon: NM_000527.5 (LDLR):c.859G>T (p.Gly287Cys), ClinVarID 251489, is classified as Pathogenic by these guidelines, therefore PM5 is met. PS3 not met: Functional data is not available.

PP3

REVEL=0.902.

PM2

PopMaxMAF=0.00003 in South Asian population in gnomAD (gnomAD v2.1.1).

PM5

One other variant at same codon: NM_000527.5 (LDLR):c.859G>T (p.Gly287Cys), ClinVarID 251489, is classified as Pathogenic by these guidelines, therefore PM5 is met.

PS3

Functional data is not available.

Approved on: 2023-04-28

Published on: 2023-04-30

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