NM_000527.5(LDLR):c.68-2A>T AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 30, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002365236.2

Allele description [Variation Report for NM_000527.5(LDLR):c.68-2A>T]

NM_000527.5(LDLR):c.68-2A>T

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.68-2A>T

HGVS:

NC_000019.10:g.11100221A>T
NG_009060.1:g.15841A>T
NM_000527.5:c.68-2A>TMANE SELECT
NM_001195798.2:c.68-2A>T
NM_001195799.2:c.68-2A>T
NM_001195800.2:c.68-2A>T
NM_001195803.2:c.68-2A>T
NM_001406861.1:c.326-2A>T
LRG_274t1:c.68-2A>T
LRG_274:g.15841A>T
NC_000019.9:g.11210897A>T
NM_000527.4:c.68-2A>T
c.68-2A>T

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001811; dbSNP: rs879254396

NCBI 1000 Genomes Browser:

rs879254396

Molecular consequence:

NM_000527.5:c.68-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195798.2:c.68-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195799.2:c.68-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195800.2:c.68-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195803.2:c.68-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406861.1:c.326-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002665243	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 30, 2016)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 10200052, 10735632, 15199436, 22698793, 22881376, 23375686 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002665243

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 30, 2016)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

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

Citations

PubMed

A novel point mutation in a splice acceptor site of intron 1 of the human low density lipoprotein receptor gene which causes severe hypercholesterolemia: an unexpected absence of exon skipping. Mutations in brief no. 139. Online.

Maruyama T, Miyake Y, Yamamura T, Tajima S, Funahashi T, Matsuzawa Y, Yamamoto A.

Hum Mutat. 1998;11(6):480-1.

PubMed [citation]

PMID:: 10200052

Molecular genetic testing for familial hypercholesterolemia: spectrum of LDL receptor gene mutations in The Netherlands.

Lombardi MP, Redeker EJ, Defesche JC, Kamerling SW, Trip MD, Mannens MM, Havekes LM, Kastelein JJ.

Clin Genet. 2000 Feb;57(2):116-24.

PubMed [citation]

PMID:: 10735632

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002665243.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The c.68-2A>T intronic pathogenic mutation results from an A to T substitution two nucleotides upstream from coding exon 2 in the LDLR gene. This alteration has been previously reported in a familial hypercholesterolemia (FH) cohort (Tichý L et al. Atherosclerosis. 2012;223:401-8). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.

#	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: May 1, 2024

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