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
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000527.5(LDLR):c.853C>T (p.His285Tyr)

CA023780

183099 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 148cae4e-2f4c-4b8c-9ba0-386e25be9821
Approved on: 2023-03-24
Published on: 2024-12-16

HGVS expressions

NM_000527.5:c.853C>T
NM_000527.5(LDLR):c.853C>T (p.His285Tyr)
NC_000019.10:g.11107427C>T
CM000681.2:g.11107427C>T
NC_000019.9:g.11218103C>T
CM000681.1:g.11218103C>T
NC_000019.8:g.11079103C>T
NG_009060.1:g.23047C>T
ENST00000252444.10:c.1111C>T
ENST00000559340.2:c.853C>T
ENST00000560467.2:c.853C>T
ENST00000558518.6:c.853C>T
ENST00000252444.9:c.1107C>T
ENST00000455727.6:c.349C>T
ENST00000535915.5:c.730C>T
ENST00000545707.5:c.472C>T
ENST00000557933.5:c.853C>T
ENST00000558013.5:c.853C>T
ENST00000558518.5:c.853C>T
ENST00000558528.1:n.368C>T
ENST00000560467.1:c.453C>T
NM_000527.4:c.853C>T
NM_001195798.1:c.853C>T
NM_001195799.1:c.730C>T
NM_001195800.1:c.349C>T
NM_001195803.1:c.472C>T
NM_001195798.2:c.853C>T
NM_001195799.2:c.730C>T
NM_001195800.2:c.349C>T
NM_001195803.2:c.472C>T
More

Uncertain Significance

Met criteria codes 2
BP4 PM2
Not Met criteria codes 23
BS1 BS4 BS3 BS2 BP7 BP3 BP1 BP2 PS1 PS2 PS3 PS4 BA1 PP1 PP2 PP3 PP4 PM6 PM1 PM3 PM5 PM4 PVS1

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.853C>T (p.His285Tyr) 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 24 March 2023. The supporting evidence is as follows: PM2: PopMax MAF = 0.00003 (0.003%) in European (Non-Finnish) exomes (gnomAD v2.1.1). BP4: REVEL= 0.489, splicing evaluation required. A.) Not on limits. B.) Does not create AG. C.) There is an AG nearby. MES scores: variant cryptic = -2.89, wt cryptic = -4.15 Cryptic scores are negative, so cryptic site is not used - variant is not predicted to alter splicing. BP4 is met.
Met criteria codes
BP4
REVEL= 0.489, splicing evaluation required. A.) Not on limits B.) Does not create AG C.) There is an AG nearby MES Scores: >variant AACAAGTTCAAGTGTTACAGCGG MAXENT: -2.89 >WT AACAAGTTCAAGTGTCACAGCGG MAXENT: -4.15 var cryptic/wt cryptic = 2.89/4.15= 0.70 var cryptic/wt score = 1.83 BP4 is met.
PM2
PopMax MAF = 0.00003 (.003%) in European (Non-Finnish) exomes (gnomAD version 2.1.1).
Not Met criteria codes
BS1
Not met.
BS4
Not met.
BS3
From PMID 25647241: in vitro microscopy assays in HeLa cells: LDLR activity similar to WT - considered as non-disruptive
BS2
Not met.
BP7
Not a synonymous variant.
BP3
Not applicable
BP1
Not applicable
BP2
Not met.
PS1
Not met.
PS2
Not met.
PS3
From PMID 25647241: in vitro microscopy assays in HeLa cells: LDLR activity similar to WT - considered as non-disruptive
PS4
Not met.
BA1
Not met.
PP1
Not met.
PP2
Not applicable
PP3
REVEL= 0.489, splicing evaluation required. Neither scenarios A, B or C are met, variant is not predicted to alter splicing.
PP4
Not met.
PM6
Not met.
PM1
Not located in exon 4 or at a cysteine residue.
PM3
Not met.
PM5
Not met.
PM4
Not an in-frame deletion or insertion.
PVS1
Not a null variant.
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.