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 label mismatch: LDLR vs undefined
  • 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.1056C>T (p.Cys352=)

CA031425

413780 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: e2aa03b0-4037-4694-9c5e-a098dab6b717
Approved on: 2025-03-28
Published on: 2025-06-04

HGVS expressions

NM_000527.5:c.1056C>T
NM_000527.5(LDLR):c.1056C>T (p.Cys352=)
NC_000019.10:g.11110767C>T
CM000681.2:g.11110767C>T
NC_000019.9:g.11221443C>T
CM000681.1:g.11221443C>T
NC_000019.8:g.11082443C>T
NG_009060.1:g.26387C>T
ENST00000252444.10:c.1314C>T
ENST00000559340.2:c.1056C>T
ENST00000560467.2:c.941-747C>T
ENST00000558518.6:c.1056C>T
ENST00000252444.9:c.1310C>T
ENST00000455727.6:c.552C>T
ENST00000535915.5:c.933C>T
ENST00000545707.5:c.675C>T
ENST00000557933.5:c.1056C>T
ENST00000558013.5:c.1056C>T
ENST00000558518.5:c.1056C>T
ENST00000560173.1:n.55C>T
ENST00000560467.1:c.541-747C>T
NM_000527.4:c.1056C>T
NM_001195798.1:c.1056C>T
NM_001195799.1:c.933C>T
NM_001195800.1:c.552C>T
NM_001195803.1:c.675C>T
NM_001195798.2:c.1056C>T
NM_001195799.2:c.933C>T
NM_001195800.2:c.552C>T
NM_001195803.2:c.675C>T
More

Benign

Met criteria codes 3
BP4 BP7 BA1
Not Met criteria codes 11
BS2 BS4 BS3 BS1 PS4 PS3 PM1 PM2 PP1 PP4 PP3

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.1056C>T (p.Cys352=) variant is classified as Benign for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes BA1, BP4 and BP7 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 28 March 2025. The supporting evidence is as follows: BA1: FAF = 0.007247 (0.7%) in East Asian exomes; since FAF ≥0.5% (gnomAD v4.1.0), BA1 is met. BP4: No REVEL score. Splicing evaluation is required. Functional data on splicing not available. A) not on limits, B) it creates a GT --- MES scores: de novo donor = -3.87, authentic donor = 5.88 --- de novo score is negative, so it is not used. Variant is not predicted to alter splicing, BP4 is met. BP7: Variant is synonymous and meets BP4.
Met criteria codes
BP4
No REVEL found. Splicing evaluation is required. Functional data on splicing not available. A) not on limits, B) it creates a GT --- MES scores: de novo donor = -3.87, authentic donor = 5.88 --- de novo score is negative, so it is not used. Variant is not predicted to alter splicing, BP4 is met.
BP7
Variant is synonymous and meets BP4.
BA1
FAF = 0.007247 (0.7%) in east asian exomes, since FAF≥0.5% (gnomAD v4.0) so BA1 is met.
Not Met criteria codes
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
not met (no information or reports of functional data).
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
not met (no information or reports of functional data).
PM1
Variant in a conserved Cys residue (Cys352), however the variant does not alter the residue and is not rare (does not meet PM2).
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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