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.1457G>A (p.Ser486Asn)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10585463

251853 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: ec4c063a-9ce4-414d-b634-eb143213bb92

Approved on: 2024-10-28

Published on: 2025-01-19

HGVS expressions

NM_000527.5:c.1457G>A

NM_000527.5(LDLR):c.1457G>A (p.Ser486Asn)

NC_000019.10:g.11113633G>A

CM000681.2:g.11113633G>A

NC_000019.9:g.11224309G>A

CM000681.1:g.11224309G>A

NC_000019.8:g.11085309G>A

NG_009060.1:g.29253G>A

ENST00000252444.10:c.1715G>A

ENST00000559340.2:c.1457G>A

ENST00000560467.2:c.1337G>A

ENST00000558518.6:c.1457G>A

ENST00000252444.9:c.1711G>A

ENST00000455727.6:c.953G>A

ENST00000535915.5:c.1334G>A

ENST00000545707.5:c.1076G>A

ENST00000557933.5:c.1457G>A

ENST00000558013.5:c.1457G>A

ENST00000558518.5:c.1457G>A

ENST00000559340.1:c.178G>A

NM_000527.4:c.1457G>A

NM_001195798.1:c.1457G>A

NM_001195799.1:c.1334G>A

NM_001195800.1:c.953G>A

NM_001195803.1:c.1076G>A

NM_001195798.2:c.1457G>A

NM_001195799.2:c.1334G>A

NM_001195800.2:c.953G>A

NM_001195803.2:c.1076G>A

Uncertain Significance

PM2 BP4

PM5 BS1 PS1 BA1 PP4 PP3

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.1457G>A (p.Ser486Asn) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 28 October 2024. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v4.1.0). BP4: REVEL = 0.297. It is below 0.5, splicing evaluation needed. Functional data on splicing not available. A) Not on limits B) Does not create a DeNovo AG or GT C) There is no GT or AG nearby. Variant is not predicted to alter splicing.

PM2

This variant is absent from gnomAD (gnomAD v4.1.0)

BP4

REVEL = 0.297. It is not above 0.75, splicing evaluation needed. Functional data on splicing not available. A) Not on limits B) Does not create a DeNovo AG or GT C) There is no GT or AG nearby Variant is not predicted to alter splicing.

PM5

1 other missense variant in the same codon: - NM_000527.5(LDLR):c.1456A>G (p.Ser486Gly) (ClinVar ID 251852) - VUS by these guidelines There are no variants in the same codon classified as Pathogenic by these guidelines.

BS1

This variant is absent from gnomAD (gnomAD v4.1.0)

PS1

There are no variants causing the same amino acid change classified as Pathogenic by these guidelines.

BA1

This variant is absent from gnomAD (gnomAD v4.1.0)

PP4

No cases identified.

PP3

Curation History

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