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NM_000527.5(LDLR):c.1845+1G>A AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 18, 2022
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:
RCV003165671.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1845+1G>A]

NM_000527.5(LDLR):c.1845+1G>A

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.1845+1G>A
Other names:
IVS12 ds G-A +1
HGVS:
  • NC_000019.10:g.11116999G>A
  • NG_009060.1:g.32619G>A
  • NM_000527.5:c.1845+1G>AMANE SELECT
  • NM_001195798.2:c.1845+1G>A
  • NM_001195799.2:c.1722+1G>A
  • NM_001195800.2:c.1341+1G>A
  • NM_001195803.2:c.1464+1G>A
  • LRG_274t1:c.1845+1G>A
  • LRG_274:g.32619G>A
  • NC_000019.9:g.11227675G>A
  • NM_000527.4:c.1845+1G>A
  • c.1845+1G>A
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000764; dbSNP: rs879255049
NCBI 1000 Genomes Browser:
rs879255049
Molecular consequence:
  • NM_000527.5:c.1845+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195798.2:c.1845+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195799.2:c.1722+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195800.2:c.1341+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195803.2:c.1464+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003912556Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Nov 18, 2022) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genetic screening of patients with familial hypercholesterolaemia (FH): a New Zealand perspective.

Laurie AD, Scott RS, George PM.

Atheroscler Suppl. 2004 Dec;5(5):13-5.

PubMed [citation]
PMID:
15556094

Effect of a splice site mutation in LDLR gene and two variations in PCSK9 gene in Tunisian families with familial hypercholesterolaemia.

Jelassi A, Slimani A, Jguirim I, Najah M, Maatouk F, Varret M, Slimane MN.

Ann Clin Biochem. 2011 Jan;48(Pt 1):83-6. doi: 10.1258/acb.2010.010087. Epub 2010 Nov 29.

PubMed [citation]
PMID:
21115573
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV003912556.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The c.1845+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 12 of the LDLR gene. This alteration, also known as FH Tunis, has been reported as heterozygous and homozygous in subjects with familial hypercholesterolemia (FH) (Jelassi A et al. Ann Clin Biochem, 2011 Jan;48:83-6; Laurie AD et al. Atheroscler Suppl, 2004 Dec;5:13-5; Dušková L et al. Atherosclerosis, 2011 May;216:139-45; Wang J et al. Arterioscler Thromb Vasc Biol, 2016 12;36:2439-2445). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024