Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000527.5(LDLR):c.211G>A (p.Gly71Arg)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA042408

375778 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

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

Uncertain Significance

PM2 BP4

PM3 PM1 PM4 PM5 PM6 BS4 BS3 BS1 BS2 PVS1 BP2 PS2 PS4 PS3 PS1 BA1 PP1 PP4 PP3

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

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.

PM2

PopMax MAF = .0001230 (.0123%) in African/African American exomes (gnomAD v 2.1.1).

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 MES Scores: denovo_variant MAXENT: 4.34 WT MAXENT: 7.07 Ratio = 4.34/7.07 = 0.61 (it is less than 0.8)

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.

BS4

Not met.

BS3

Not met.

BS1

Not met.

BS2

Not met.

PVS1

Not a null variant.

BP2

Not met.

PS2

Not met.

PS4

Not met.

PS3

Not met.

PS1

Not met.

BA1

Not met.

PP1

Not met.

PP4

Not met.

PP3

REVEL= 0.45, splicing evaluation required.

Curation History

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