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

Variant: NM_000527.5(LDLR):c.242G>A (p.Arg81His)

CA404075600

924271 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 5a3fa832-03e0-401e-89cd-97844d4d7bfa

HGVS expressions

NM_000527.5:c.242G>A
NM_000527.5(LDLR):c.242G>A (p.Arg81His)
NC_000019.10:g.11102715G>A
CM000681.2:g.11102715G>A
NC_000019.9:g.11213391G>A
CM000681.1:g.11213391G>A
NC_000019.8:g.11074391G>A
NG_009060.1:g.18335G>A
ENST00000558518.6:c.242G>A
ENST00000252444.9:n.496G>A
ENST00000455727.6:c.242G>A
ENST00000535915.5:c.190+2370G>A
ENST00000545707.5:c.242G>A
ENST00000557933.5:c.242G>A
ENST00000557958.1:n.328G>A
ENST00000558013.5:c.242G>A
ENST00000558518.5:c.242G>A
NM_000527.4:c.242G>A
NM_001195798.1:c.242G>A
NM_001195799.1:c.190+2370G>A
NM_001195800.1:c.242G>A
NM_001195803.1:c.242G>A
NM_001195798.2:c.242G>A
NM_001195799.2:c.190+2370G>A
NM_001195800.2:c.242G>A
NM_001195803.2:c.242G>A

Uncertain Significance

Met criteria codes 1
PM2
Not Met criteria codes 25
PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PM6 PM4 PM3 PM1 PM5 PVS1 BA1 BS2 BS4 BS3 BS1 BP7 BP5 BP3 BP2 BP4 BP1

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR): c.242G>A (p.Arg81His) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence code PM2 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2 - PopMax MAF = 0.00004005 (0.004%) in African/African American exomes+genomes (gnomAD v2.1.1).
Met criteria codes
PM2
PopMax MAF = 0.00004005 (0.004%) in African/African American exomes+genomes (gnomAD v2.1.1)
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
REVEL = 0.564
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
2 other missense variants in the same codon: - NM_000527.5(LDLR):c.241C>A (p.Arg81Ser)(ClinVar ID 251088) - Uncertain significance by these guidelines - NM_000527.5(LDLR):c.241C>T (p.Arg81Cys)(ClinVar ID 183083) - Likely pathogenic by these guidelines There is no variant in the same codon classified as Pathogenic by these guidelines.
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
REVEL = 0.564
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2023-04-28
Published on: 2023-05-01
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