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.908G>A (p.Arg303Gln)

CA023789

183101 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 6c22a5ef-a868-4c62-8d52-d83c27c7e7b4

HGVS expressions

NM_000527.5:c.908G>A
NM_000527.5(LDLR):c.908G>A (p.Arg303Gln)
NC_000019.10:g.11107482G>A
CM000681.2:g.11107482G>A
NC_000019.9:g.11218158G>A
CM000681.1:g.11218158G>A
NC_000019.8:g.11079158G>A
NG_009060.1:g.23102G>A
ENST00000558518.6:c.908G>A
ENST00000252444.9:n.1162G>A
ENST00000455727.6:c.404G>A
ENST00000535915.5:c.785G>A
ENST00000545707.5:c.527G>A
ENST00000557933.5:c.908G>A
ENST00000558013.5:c.908G>A
ENST00000558518.5:c.908G>A
ENST00000558528.1:n.423G>A
ENST00000560467.1:n.508G>A
NM_000527.4:c.908G>A
NM_001195798.1:c.908G>A
NM_001195799.1:c.785G>A
NM_001195800.1:c.404G>A
NM_001195803.1:c.527G>A
NM_001195798.2:c.908G>A
NM_001195799.2:c.785G>A
NM_001195800.2:c.404G>A
NM_001195803.2:c.527G>A

Uncertain Significance

Met criteria codes 2
PM2 BP4
Not Met criteria codes 24
PS2 PS4 PS3 PS1 PVS1 PP4 PP1 PP3 PP2 BA1 PM6 BS4 BS3 BS1 PM3 PM4 PM1 PM5 BS2 BP5 BP7 BP2 BP3 BP1

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.908G>A (p.Arg303Gln) variant is classified as variant of Uncertain significance for Familial Hypercholesterolemia by applying evidence codes (PM2 and BP4) 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 = 0.00004627 (0.004627%) in European (Finnish) exomes+genomes (gnomAD v2.1.1). BP4 - REVEL = 0.294. It is below 0.5, splicing evaluation required. Functional data on splicing not available. Variant is exonic and at least 50bp downstream from canonical acceptor site but it does not create GT. Variant is not predicted to alter splicing.
Met criteria codes
PM2
PopMax MAF = 0.00004627 (0.004627%) in European (Finnish) exomes+genomes (gnomAD v2.1.1).
BP4
REVEL = 0.294. It is below 0.5, splicing evaluation required. Functional data on splicing not available. Variant is exonic and at least 50bp downstream from canonical acceptor site but it does not create GT. Variant is not predicted to alter splicing.
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
PVS1
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
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
PM6
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
PM3
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
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
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
BP5
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
BP2
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
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2022-01-19
Published on: 2022-06-30
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