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
  • There was no gene found in the curated document received from the VCI/VCEP
  • Gene listed was thus derived from ClinVar and/or CAR
  • No CSPEC related information was provided by the message!
  • See Evidence submitted by expert panel for details.

CA10584700

250946 (ClinVar)

Gene: N/A
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 1ad04294-299b-4ea4-b379-ae8587279e15

HGVS expressions

NC_000019.10:g.11089400C>A
CM000681.2:g.11089400C>A
NC_000019.9:g.11200076C>A
CM000681.1:g.11200076C>A
NC_000019.8:g.11061076C>A
NG_009060.1:g.5020C>A
ENST00000558518.5:c.-149C>A
NM_000527.4:c.-149C>A
NM_001195798.1:c.-149C>A
NM_001195799.1:c.-149C>A
NM_001195800.1:c.-149C>A
NM_001195803.1:c.-149C>A
NR_163945.1:n.260G>T
NM_000527.4(LDLR):c.-149C>A

Likely Pathogenic

Met criteria codes 4
PS4 PP4 PP1_Moderate PM2
Not Met criteria codes 18
PS1 PS2 PS3 PVS1 PP3 BA1 PM6 BS4 BS3 BS1 PM1 PM3 PM4 PM5 BS2 BP7 BP2 BP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.4(LDLR):c.-149C>A variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes (PM2, PS4, PP4, PP1_moderate) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PM2 - This variant is absent from gnomAD (gnomAD v2.1.1), so PM2 is Met. PS4 - Variant meets PM2 and is identified in 10 unrelated index cases who fulfill Simon Broome criteria for FH (4 definite FH and 6 possible FH) from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation)(PMID: 28379029), so PS4 is Met. PP4 - Variant meets PM2 and is identified in 10 unrelated index cases who fulfill Simon Broome criteria for FH (see PS4 for details), so PP4 is Met. PP1_Moderate - Variant segregates with FH phenotype in 4 informative meiosis from 3 families from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation)(PMID: 28379029), so PP1_Moderate is Met.
Met criteria codes
PS4
Variant meets PM2 and is identified in 10 unrelated index cases who fulfill Simon Broome criteria for FH (4 definite FH and 6 possible FH) from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation)(PMID: 28379029), so PS4 is Met.
PP4
Variant meets PM2 and is identified in 10 unrelated index cases who fulfill Simon Broome criteria for FH (4 definite FH and 6 possible FH) from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation)(PMID: 28379029), so PP4 is Met.
PP1_Moderate
Variant segregates with FH phenotype in 4 informative meiosis from 3 families from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation)(PMID: 28379029), so PP1_Moderate is Met.
PM2
This variant is absent from gnomAD (gnomAD v2.1.1), so PM2 is Met.
Not Met criteria codes
PS1
Variant is not missense, so PS1 is not met.
PS2
de novo occurrence data not reported, so PS2 is Not Met.
PS3
There are no functional studies reported for this variant, so PS3 is not met.
PVS1
Variant is on 5'UTR, so PVS1 is Not Met.
PP3
Variant is on 5'UTR, so PP3 is Not Met.
BA1
No population data was found for this variant in gnomAD (gnomAD v2.1.1), so BA1 is Not Met.
PM6
de novo occurrence data not reported, so PM6 is Not Met.
BS4
Lack of segregation data not reported, so BS4 is Not Met.
BS3
There are no functional studies reported for this variant, so BS3 is not met.
BS1
No population data was found for this variant in gnomAD (gnomAD v2.1.1), so BS1 is Not Met.
PM1
Variant meets PM2 but is not missense, so PM1 is Not Met.
PM3
Not observed in trans with other LP/P variants, so PM3 is Not Met.
PM4
Variant meets PM2 but is on 5'UTR, so PM4 is Not Met.
PM5
Variant is not missense, so PM5 is not met.
BS2
Not observed in 100 normolipidemic individuals from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation), so BS2 is Not Met.
BP7
Variant is not synonymous, so BP7 is Not Met.
BP2
Not observed in trans with other LP/P variants, so BP2 is Not Met.
BP4
Variant is on 5'UTR, so BP4 is Not Met.
Approved on: 2022-08-29
Published on: 2022-12-23
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