NM_000527.5(LDLR):c.941-2A>C AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 29, 2021
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:: RCV001854896.4

Allele description [Variation Report for NM_000527.5(LDLR):c.941-2A>C]

NM_000527.5(LDLR):c.941-2A>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.941-2A>C

HGVS:

NC_000019.10:g.11110650A>C
NG_009060.1:g.26270A>C
NM_000527.5:c.941-2A>CMANE SELECT
NM_001195798.2:c.941-2A>C
NM_001195799.2:c.818-2A>C
NM_001195800.2:c.437-2A>C
NM_001195803.2:c.560-2A>C
LRG_274:g.26270A>C
NC_000019.9:g.11221326A>C
c.941-2A>C

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000141; dbSNP: rs112366278

NCBI 1000 Genomes Browser:

rs112366278

Molecular consequence:

NM_000527.5:c.941-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195798.2:c.941-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195799.2:c.818-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195800.2:c.437-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001195803.2:c.560-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Familial hypercholesterolemia
Identifiers:: MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

Recent activity

Clear Turn Off Turn On

Trgv7 T cell receptor gamma, variable 7 [Mus musculus]
Trgv7 T cell receptor gamma, variable 7 [Mus musculus]
Gene ID:21641

Gene
Homologene neighbors for GEO Profiles (Select 44335273) (0)
GEO Profiles
Profile neighbors for GEO Profiles (Select 44335908) (66)
GEO Profiles
Homo sapiens
Homo sapiens
RefSeq annotation of the human reference genome assembly

BioProject
BioProject Links for Nucleotide (Select 2217298654) (1)
BioProject

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002172701	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 29, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12436241, 15359125, 20145306, 16199547, 20809525, 28645073, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002172701

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 29, 2021)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

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

Intronic mutations outside of Alu-repeat-rich domains of the LDL receptor gene are a cause of familial hypercholesterolemia.

Amsellem S, Briffaut D, Carrié A, Rabès JP, Girardet JP, Fredenrich A, Moulin P, Krempf M, Reznik Y, Vialettes B, de Gennes JL, Brukert E, Benlian P.

Hum Genet. 2002 Dec;111(6):501-10. Epub 2002 Sep 13.

PubMed [citation]

PMID:: 12436241

Novel and recurrent mutations of the LDL receptor gene in Korean patients with familial hypercholesterolemia.

Kim JH, Choi HK, Lee H, Park HY, Kim JH, Kim JW, Kim HJ, Lee ST.

Mol Cells. 2004 Aug 31;18(1):63-70.

PubMed [citation]

PMID:: 15359125

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002172701.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

ClinVar contains an entry for this variant (Variation ID: 251553). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with familial hypercholesterolemia (PMID: 12436241, 15359125, 20145306). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 6 of the LDLR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073).

#	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

ClinVar

Relating variation to medicine