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]
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  • See Evidence submitted by expert panel for details.

Variant: NM_000527.5(LDLR):c.2101G>A (p.Gly701Ser)

CA023635

183130 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 4ce3f966-2bbf-4b29-ad24-d066a9b9ef76

HGVS expressions

NM_000527.5:c.2101G>A
NM_000527.5(LDLR):c.2101G>A (p.Gly701Ser)
ENST00000558518.6:c.2101G>A
ENST00000252444.9:n.2355G>A
ENST00000455727.6:c.1597G>A
ENST00000535915.5:c.1978G>A
ENST00000545707.5:c.1606+250G>A
ENST00000557933.5:c.2101G>A
ENST00000558013.5:c.2101G>A
ENST00000558518.5:c.2101G>A
NM_000527.4:c.2101G>A
NM_001195798.1:c.2101G>A
NM_001195799.1:c.1978G>A
NM_001195800.1:c.1597G>A
NM_001195803.1:c.1606+250G>A
NM_001195798.2:c.2101G>A
NM_001195799.2:c.1978G>A
NM_001195800.2:c.1597G>A
NM_001195803.2:c.1606+250G>A
NC_000019.10:g.11120483G>A
CM000681.2:g.11120483G>A
NC_000019.9:g.11231159G>A
CM000681.1:g.11231159G>A
NC_000019.8:g.11092159G>A
NG_009060.1:g.36103G>A

Uncertain Significance

Met criteria codes 2
PP3 PP1_Moderate
Not Met criteria codes 24
PVS1 BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS4 PS3 PS1 BA1 PP4 PP2 PM6 PM2 PM3 PM1 PM4 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
NM_000527.5(LDLR):c.2101G>A (p.Gly701Ser) variant is classified as variant of Uncertain significance for Familial Hypercholesterolemia by applying evidence codes (PP1_Moderate and PP3) 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: PP1_moderate - Variant segregates with FH phenotype in 4 informative meioses in 2 families from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation). PP3 - REVEL: 0,754.
Met criteria codes
PP3
REVEL: 0,754. Score is above 0,75.
PP1_Moderate
Variant segregates with FH phenotype in 4 informative meioses in 2 families from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation).
Not Met criteria codes
PVS1
Missense variant. Not applicable.
BS2
No unaffected individuals identified with the variant.
BS4
No non-segregations were identified/found.
BS3
No functional assays performed/found - not applicable.
BS1
FAF = 0.0002447 (0.02447%) in Latino exomes (gnomAD v2.1.1). FAF is not above 0.2%.
BP5
Not applicable.
BP7
Missense variant. Not applicable.
BP2
Not identified in individuals with other variants.
BP3
Not applicable.
BP4
REVEL: 0,754. Score is not below 0,50.
BP1
Not applicable.
PS2
No de novo cases were identified.
PS4
PM2 is not met. Not applicable.
PS3
No functional assays performed/found - not applicable.
PS1
No variant described that leads to the same amino acid change.
BA1
FAF = 0.0002447 (0.02447%) in Latino exomes (gnomAD v2.1.1). FAF is not above 0.5%
PP4
PM2 is not met. Not applicable.
PP2
Not applicable.
PM6
No de novo cases were identified.
PM2
PopMax MAF = 0.0004233 (0.042%) in Latino exomes (gnomAD v2.1.1). MAF is not below 0.02%.
PM3
Not identified in individuals with other variants.
PM1
Missense at codon 701 - it is not exon 4 or any of the 60 Cys residues listed and does not meet PM2. Not applicable.
PM4
Missense variant. Not applicable.
PM5
No other variant found in this codon in ClinVar database (assessed 4 June 2020).
Approved on: 2021-06-18
Published on: 2021-06-24
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