NM_000527.5(LDLR):c.314-2A>C AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Nov 8, 2022
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:: RCV000237624.7

Allele description [Variation Report for NM_000527.5(LDLR):c.314-2A>C]

NM_000527.5(LDLR):c.314-2A>C

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.314-2A>C

Other names:

IVS3 as A-C -2

HGVS:

NC_000019.10:g.11105218A>C
NG_009060.1:g.20838A>C
NG_140410.1:g.435A>C
NM_000527.5:c.314-2A>CMANE SELECT
NM_001195798.2:c.314-2A>C
NM_001195799.2:c.191-2A>C
NM_001195800.2:c.314-2174A>C
NM_001195803.2:c.314-1347A>C
LRG_274t1:c.314-2A>C
LRG_274:g.20838A>C
NC_000019.9:g.11215894A>C
NM_000527.4:c.314-2A>C
c.314-2A>C

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000982; dbSNP: rs879254470

NCBI 1000 Genomes Browser:

rs879254470

Molecular consequence:

NM_001195800.2:c.314-2174A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1347A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.314-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195798.2:c.314-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195799.2:c.191-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Observations:

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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mitochondrial carrier [Mollisia scopiformis]
mitochondrial carrier [Mollisia scopiformis]
gi|1069189992|ref|XP_018065019.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000294616	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,
SCV000484777	Robarts Research Institute, Western University	criteria provided, single submitter (Wang et al. (Arterioscler Thromb Vasc Biol. 2016))	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003827817	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 8, 2022)	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

SCV000294616

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,

SCV000484777

Robarts Research Institute, Western University

criteria provided, single submitter

(Wang et al. (Arterioscler Thromb Vasc Biol. 2016))

Likely pathogenic

germline

clinical testing

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

SCV003827817

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 8, 2022)

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	yes	6	not provided	not provided	1	not provided	clinical testing, literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Low density lipoprotein receptor (LDLR) gene mutations in Canadian subjects with familial hypercholesterolemia, but not of French descent.

Wang J, Huff E, Janecka L, Hegele RA.

Hum Mutat. 2001 Oct;18(4):359.

PubMed [citation]

PMID:: 11668627

Polygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically.

Wang J, Dron JS, Ban MR, Robinson JF, McIntyre AD, Alazzam M, Zhao PJ, Dilliott AA, Cao H, Huff MW, Rhainds D, Low-Kam C, Dubé MP, Lettre G, Tardif JC, Hegele RA.

Arterioscler Thromb Vasc Biol. 2016 Dec;36(12):2439-2445. Epub 2016 Oct 20.

PubMed [citation]

PMID:: 27765764

See all PubMed Citations (3)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000294616.2

#	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 Robarts Research Institute, Western University, SCV000484777.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	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	yes	not provided	not provided	not provided		5	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003827817.2

#	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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