NM_000527.5(LDLR):c.1187-2A>G AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jun 14, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000237447.4

Allele description [Variation Report for NM_000527.5(LDLR):c.1187-2A>G]

NM_000527.5(LDLR):c.1187-2A>G

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.1187-2A>G

HGVS:

NC_000019.10:g.11113276A>G
NG_009060.1:g.28896A>G
NM_000527.5:c.1187-2A>GMANE SELECT
NM_001195798.2:c.1187-2A>G
NM_001195799.2:c.1064-2A>G
NM_001195800.2:c.683-2A>G
NM_001195803.2:c.806-2A>G
LRG_274t1:c.1187-2A>G
LRG_274:g.28896A>G
NC_000019.9:g.11223952A>G
NM_000527.4:c.1187-2A>G
c.1187-2A>G

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000175; dbSNP: rs879254823

NCBI 1000 Genomes Browser:

rs879254823

Molecular consequence:

NM_000527.5:c.1187-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195798.2:c.1187-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195799.2:c.1064-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195800.2:c.683-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195803.2:c.806-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Hypercholesterolemia, familial, 1
Synonyms:: LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

Recent activity

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transmembrane protein, putative (DUF677) [Arabidopsis thaliana]
transmembrane protein, putative (DUF677) [Arabidopsis thaliana]
gi|15229080|ref|NP_190476.1|

Protein
B3GNT2 [Mandrillus leucophaeus]
B3GNT2 [Mandrillus leucophaeus]
Gene ID:105544724

Gene
Amphibalanus amphitrite
Amphibalanus amphitrite
Amphibalanus amphitrite Genome sequencing and assembly

BioProject
BioProject Links for Nucleotide (Select 2704707780) (1)
BioProject
RefSeq Protein Links for Gene (Select 83851) (28)
Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295274	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Likely pathogenic (Mar 25, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000599366	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2016)	germline, not applicable	curation, literature only	PubMed (2) [See all records that cite these PMIDs] 25741868, 19208450
SCV004237269	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 14, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000295274

LDLR-LOVD, British Heart Foundation

criteria provided, single submitter

(ACGS Guidelines, 2013)

Likely pathogenic
(Mar 25, 2016)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV000599366

Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 1, 2016)

germline, not applicable

curation, literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV004237269

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 14, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation
not provided	germline	yes	1	not provided	not provided	1	not provided	literature only
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Low-density lipoprotein receptor gene familial hypercholesterolemia variant database: update and pathological assessment.

Usifo E, Leigh SE, Whittall RA, Lench N, Taylor A, Yeats C, Orengo CA, Martin AC, Celli J, Humphries SE.

Ann Hum Genet. 2012 Sep;76(5):387-401. doi: 10.1111/j.1469-1809.2012.00724.x.

PubMed [citation]

PMID:: 22881376

Effects of intronic mutations in the LDLR gene on pre-mRNA splicing: Comparison of wet-lab and bioinformatics analyses.

Holla ØL, Nakken S, Mattingsdal M, Ranheim T, Berge KE, Defesche JC, Leren TP.

Mol Genet Metab. 2009 Apr;96(4):245-52. doi: 10.1016/j.ymgme.2008.12.014. Epub 2009 Feb 10.

PubMed [citation]

PMID:: 19208450

See all PubMed Citations (3)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295274.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	literature only	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000599366.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)
2	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

"Assay Description:Htz patients' Epstein Barr virus transformed lymphocytes, RNA assays"

PubMed [ID: 19208450]

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided
2	not applicable	not applicable	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV004237269.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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