Evidence Repository
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

Variant: NM_000527.5(LDLR):c.507C>T (p.Asn169=)

CA023711

36464 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 3d40bc8b-8ea2-4ed8-8632-ba1d9aad97e1
Approved on: 2025-01-31
Published on: 2025-02-27

HGVS expressions

NM_000527.5:c.507C>T
NM_000527.5(LDLR):c.507C>T (p.Asn169=)
NC_000019.10:g.11105413C>T
CM000681.2:g.11105413C>T
NC_000019.9:g.11216089C>T
CM000681.1:g.11216089C>T
NC_000019.8:g.11077089C>T
NG_009060.1:g.21033C>T
ENST00000252444.10:c.765C>T
ENST00000559340.2:c.507C>T
ENST00000560467.2:c.507C>T
ENST00000558518.6:c.507C>T
ENST00000252444.9:c.761C>T
ENST00000455727.6:c.314-1979C>T
ENST00000535915.5:c.384C>T
ENST00000545707.5:c.314-1152C>T
ENST00000557933.5:c.507C>T
ENST00000558013.5:c.507C>T
ENST00000558518.5:c.507C>T
ENST00000560467.1:c.107C>T
NM_000527.4:c.507C>T
NM_001195798.1:c.507C>T
NM_001195799.1:c.384C>T
NM_001195800.1:c.314-1979C>T
NM_001195803.1:c.314-1152C>T
NM_001195798.2:c.507C>T
NM_001195799.2:c.384C>T
NM_001195800.2:c.314-1979C>T
NM_001195803.2:c.314-1152C>T
More

Likely Benign

Met criteria codes 2
BP4 BP7
Not Met criteria codes 4
PP4 PM2 BA1 BS1

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.507C>T (p.Asn169=) variant is classified as Likely Benign for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes BP4 and BP7 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 31 January 2025. The supporting evidence is as follows: BP4: No REVEL, splicing evaluation required. Functional data on splicing not available. A) not on limits; B) does not create AG/GT; C) there is an AG nearby. MES scores: variant cryptic = -0.72, wt cryptic = -0.20, canonical acceptor = 8.16. Ratio variant cryptic/wt cryptic: -0.72/-0.20 = 3.6 --- it is above 1.1. Ratio variant cryptic/canonical acceptor: -0.72/8.16 = -0.09 --- it is not above 0.9. Variant is not predicted to alter splicing. PP3 is not met. BP4 is met. BP7: Variant is synonymous and meets BP4.
Met criteria codes
BP4
No REVEL, splicing evaluation required. Functional data on splicing not available. A) not on limits; B) does not create AG/GT; C) there is an AG nearby. MES scores: variant cryptic = -0.72, wt cryptic = -0.20, canonical acceptor = 8.16. Ratio variant cryptic/wt cryptic: -0.72/-0.20 = 3.6 --- it is above 1.1. Ratio variant cryptic/canonical acceptor: -0.72/8.16 = -0.09 --- it is not above 0.9. Variant is not predicted to alter splicing. PP3 is not met. BP4 is met.
BP7
Variant is synonymous and meets BP4.
Not Met criteria codes
PP4
Although the variant was idenitifed in one index case meeting DLCN >=6 (Research Lab of Molecular Genetics of Lipid Metabolism), that variant does not meet PM2.
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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