The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000527.5(LDLR):c.1456A>G (p.Ser486Gly)

CA10585462

251852 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
UUID: 0f596a5c-c0a3-4bb1-a634-d93b1af46fc5
Approved on: 2024-10-28
Published on: 2025-01-19

HGVS expressions

NM_000527.5:c.1456A>G
NM_000527.5(LDLR):c.1456A>G (p.Ser486Gly)
NC_000019.10:g.11113632A>G
CM000681.2:g.11113632A>G
NC_000019.9:g.11224308A>G
CM000681.1:g.11224308A>G
NC_000019.8:g.11085308A>G
NG_009060.1:g.29252A>G
ENST00000252444.10:c.1714A>G
ENST00000559340.2:c.1456A>G
ENST00000560467.2:c.1336A>G
ENST00000558518.6:c.1456A>G
ENST00000252444.9:c.1710A>G
ENST00000455727.6:c.952A>G
ENST00000535915.5:c.1333A>G
ENST00000545707.5:c.1075A>G
ENST00000557933.5:c.1456A>G
ENST00000558013.5:c.1456A>G
ENST00000558518.5:c.1456A>G
ENST00000559340.1:c.177A>G
NM_000527.4:c.1456A>G
NM_001195798.1:c.1456A>G
NM_001195799.1:c.1333A>G
NM_001195800.1:c.952A>G
NM_001195803.1:c.1075A>G
NM_001195798.2:c.1456A>G
NM_001195799.2:c.1333A>G
NM_001195800.2:c.952A>G
NM_001195803.2:c.1075A>G
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Uncertain Significance

Met criteria codes 1
PM2
Not Met criteria codes 7
BA1 BS1 BP4 PS1 PP4 PP3 PM5

Evidence Links 0

Expert Panel

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.1456A>G (p.Ser486Gly) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence code PM2 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).
Met criteria codes
PM2
This variant is absent from gnomAD (gnomAD v4.1.0)
Not Met criteria codes
BA1
This variant is absent from gnomAD (gnomAD v4.1.0)
BS1
This variant is absent from gnomAD (gnomAD v4.1.0)
BP4
REVEL = 0.504. It is not below 0.5.
PS1
There are no variants causing the same amino acid change classified as Pathogenic by these guidelines.
PP4
No cases identified.
PP3
REVEL = 0.504. 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.1457G>A (p.Ser486Asn) (ClinVar ID 251853) - VUS by these guidelines There are no variants in the same codon classified as Pathogenic by these guidelines.
Curation History
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