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]
Link to SEPIO compliant JSON-LD document
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000527.5(LDLR):c.479G>A (p.Cys160Tyr)

CA10584941

251249 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 048c4ff0-fa24-4f42-8889-f524ace1f7de
Approved on: 2024-02-23
Published on: 2024-09-25

HGVS expressions

NM_000527.5:c.479G>A
NM_000527.5(LDLR):c.479G>A (p.Cys160Tyr)
NC_000019.10:g.11105385G>A
CM000681.2:g.11105385G>A
NC_000019.9:g.11216061G>A
CM000681.1:g.11216061G>A
NC_000019.8:g.11077061G>A
NG_009060.1:g.21005G>A
ENST00000252444.10:c.737G>A
ENST00000559340.2:c.479G>A
ENST00000560467.2:c.479G>A
ENST00000558518.6:c.479G>A
ENST00000252444.9:c.733G>A
ENST00000455727.6:c.314-2007G>A
ENST00000535915.5:c.356G>A
ENST00000545707.5:c.314-1180G>A
ENST00000557933.5:c.479G>A
ENST00000558013.5:c.479G>A
ENST00000558518.5:c.479G>A
ENST00000560467.1:c.79G>A
NM_000527.4:c.479G>A
NM_001195798.1:c.479G>A
NM_001195799.1:c.356G>A
NM_001195800.1:c.314-2007G>A
NM_001195803.1:c.314-1180G>A
NM_001195798.2:c.479G>A
NM_001195799.2:c.356G>A
NM_001195800.2:c.314-2007G>A
NM_001195803.2:c.314-1180G>A

Uncertain Significance

Met criteria codes 3
PP3 PM2 PM1
Not Met criteria codes 19
PP4 PP1 BA1 PM6 PM3 PM4 PM5 BS2 BS4 BS3 BS1 PS2 PS4 PS3 PS1 BP2 BP3 BP4 PVS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.479G>A (p.Cys160Tyr) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM1, PM2 and PP3 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 23 February 2024. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v2.1.1). PP3: REVEL=0.936. PM1: Variant meets PM2, is a missense in exon 4, and alters Cys160, one of the cysteine residues listed.
Met criteria codes
PP3
REVEL=0.936. It is >0.75, so PP3 is met.
PM2
This variant is absent from gnomAD (gnomAD v2.1.1). So, PM2 is met.
PM1
Variant meets PM2, is in exon 4 (missense at codon 160), and alters Cys160, one of the cysteine residues listed. So, PM1 is met.
Not Met criteria codes
PP4
No data available
PP1
2 family members without the variants and normal LDL, but no affected family member with the variant was detected.
BA1
This variant is absent from gnomAD (gnomAD v2.1.1).
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No data available
PM4
No in-frame deletions/insertions
PM5
4 other missense variants in the same codon: - NM_000527.5(LDLR):c.478T>A (p.Cys160Ser) (ClinVar ID 977991) - Likely Pathogenic by these guidelines - NM_000527.5(LDLR):c.478T>G (p.Cys160Gly) (ClinVar ID 251248) - Pathogenic/Likely pathogenic by these guidelines - NM_000527.5(LDLR):c.478T>C (p.Cys160Arg) (ClinVar ID 251247) - Pathogenic/Likely pathogenic by these guidelines - NM_000527.5(LDLR):c.479G>T (p.Cys160Phe) (ClinVar ID 441187) - Likely pathogenic by these guidelines There is no variant in the same codon classified as Pathogenic by these guidelines.
BS2
No data available.
BS4
lack of co-segregation in only 1 family member
BS3
No data available.
BS1
This variant is absent from gnomAD (gnomAD v2.1.1).
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Variants meet PM2, but is identified in 1 patient.
PS3
No data available.
PS1
No other missense variant in the same codon with the same amino acid change
BP2
No data available
BP3
No in-frame deletions/insertions
BP4
REVEL=0.936. It is >0.5.
PVS1
Not a null variant (nonsense, frameshift, canonical +/- 1 or 2 splice sites, initiation codon, single or multiexon deletion)
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.