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.1845+15C>A

CA10585649

252071 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 081573c3-4f5c-47c2-b9ea-8ce4e830fe2a

HGVS expressions

NM_000527.5:c.1845+15C>A
NM_000527.5(LDLR):c.1845+15C>A
NC_000019.10:g.11117013C>A
CM000681.2:g.11117013C>A
NC_000019.9:g.11227689C>A
CM000681.1:g.11227689C>A
NC_000019.8:g.11088689C>A
NG_009060.1:g.32633C>A
ENST00000558518.6:c.1845+15C>A
ENST00000252444.9:n.2099+15C>A
ENST00000455727.6:c.1341+15C>A
ENST00000535915.5:c.1722+15C>A
ENST00000545707.5:c.1464+15C>A
ENST00000557933.5:c.1845+15C>A
ENST00000558013.5:c.1845+15C>A
ENST00000558518.5:c.1845+15C>A
ENST00000559340.1:n.426+801C>A
NM_000527.4:c.1845+15C>A
NM_001195798.1:c.1845+15C>A
NM_001195799.1:c.1722+15C>A
NM_001195800.1:c.1341+15C>A
NM_001195803.1:c.1464+15C>A
NM_001195798.2:c.1845+15C>A
NM_001195799.2:c.1722+15C>A
NM_001195800.2:c.1341+15C>A
NM_001195803.2:c.1464+15C>A

Uncertain Significance

Met criteria codes 2
PM2 PM3
Not Met criteria codes 24
PS2 PS4 PS3 PS1 PVS1 PP4 PP1 PP3 PP2 BA1 PM6 BS4 BS3 BS1 PM1 PM4 PM5 BS2 BP5 BP7 BP2 BP3 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 1.1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.1845+15C>A variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2 and PM3) 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: PM2 - This variant is absent from gnomAD (gnomAD v2.1.1). PM3 - Variant meets PM2 and is identified in an index case published in PMID: 30269829 with homozygous FH phenotype (LDL-C = 14.5 mmol/l) and also duplication of whole PCSK9 gene, classified as Pathogenic by the general ACMG guidelines.
Met criteria codes
PM2
This variant is absent from gnomAD (gnomAD v2.1.1).
PM3
Variant meets PM2 and is identified in an index case published in PMID: 30269829 with homozygous FH phenotype (LDL-C = 14.5 mmol/l) and also duplication of whole PCSK9 gene, classified as Pathogenic by the general ACMG guidelines.
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 REVEL, splicing evaluation needed. Functional data on splicing not available. A) variant not on limits. B) variant is not exonic. C) variant is not exonic.
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
PM1
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
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
BP4
No REVEL, splicing evaluation needed. Functional data on splicing not available. A) variant not on limits. B) variant is not exonic. C) variant is not exonic.
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2022-07-22
Published on: 2022-12-23
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