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.211G>A (p.Gly71Arg)

CA042408

375778 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
UUID: 320c3f6b-2c64-4c1f-ae3b-00d74a35c5e1
Approved on: 2023-03-24
Published on: 2024-12-18

HGVS expressions

NM_000527.5:c.211G>A
NM_000527.5(LDLR):c.211G>A (p.Gly71Arg)
NC_000019.10:g.11102684G>A
CM000681.2:g.11102684G>A
NC_000019.9:g.11213360G>A
CM000681.1:g.11213360G>A
NC_000019.8:g.11074360G>A
NG_009060.1:g.18304G>A
ENST00000252444.10:c.469G>A
ENST00000559340.2:c.211G>A
ENST00000560467.2:c.211G>A
ENST00000558518.6:c.211G>A
ENST00000252444.9:c.465G>A
ENST00000455727.6:c.211G>A
ENST00000535915.5:c.190+2339G>A
ENST00000545707.5:c.211G>A
ENST00000557933.5:c.211G>A
ENST00000557958.1:n.297G>A
ENST00000558013.5:c.211G>A
ENST00000558518.5:c.211G>A
NM_000527.4:c.211G>A
NM_001195798.1:c.211G>A
NM_001195799.1:c.190+2339G>A
NM_001195800.1:c.211G>A
NM_001195803.1:c.211G>A
NM_001195798.2:c.211G>A
NM_001195799.2:c.190+2339G>A
NM_001195800.2:c.211G>A
NM_001195803.2:c.211G>A
More

Uncertain Significance

Met criteria codes 2
BP4 PM2
Not Met criteria codes 19
PS2 PS4 PS3 PS1 BP2 PP1 PP4 PP3 PVS1 PM3 PM1 PM4 PM5 PM6 BA1 BS4 BS3 BS1 BS2

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.211G>A (p.Gly71Arg) 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 = 0.0001230 (0.0123%) in African/African American exomes (gnomAD v2.1.1). BP4: REVEL= 0.45, splicing evaluation required. A) variant not on limits B) variant is exonic and at least 50bp upstream/downstream from canonical donor/acceptor site and creates AG. Score in MES: denovo_variant = 4.34. WT = 7.07. Ratio = 4.34/7.07 = 0.61 (less than 0.8). Variant is not predicted to alter splicing.
Met criteria codes
BP4
REVEL= 0.45, splicing evaluation required. A) variant not on limits B) variant is exonic and at least 50bp upstream/downstream from canonical donor/acceptor site and creates AG MES Scores: denovo_variant MAXENT: 4.34 WT MAXENT: 7.07 Ratio = 4.34/7.07 = 0.61 (it is less than 0.8)
PM2
PopMax MAF = .0001230 (.0123%) in African/African American exomes (gnomAD v 2.1.1).
Not Met criteria codes
PS2
Not met.
PS4
Not met.
PS3
Not met.
PS1
Not met.
BP2
Not met.
PP1
Not met.
PP4
Not met.
PP3
REVEL= 0.45, splicing evaluation required.
PVS1
Not a null variant.
PM3
Not met.
PM1
Not located in exon 4 or at a cysteine residue.
PM4
Not an in-frame deletion/insertion.
PM5
Not met.
PM6
Not met.
BA1
Not met.
BS4
Not met.
BS3
Not met.
BS1
Not met.
BS2
Not met.
Curation History
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