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NM_000527.5(LDLR):c.1358+2T>A AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 9, 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:
RCV002381272.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1358+2T>A]

NM_000527.5(LDLR):c.1358+2T>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.1358+2T>A
HGVS:
  • NC_000019.10:g.11113451T>A
  • NG_009060.1:g.29071T>A
  • NM_000527.5:c.1358+2T>AMANE SELECT
  • NM_001195798.2:c.1358+2T>A
  • NM_001195799.2:c.1235+2T>A
  • NM_001195800.2:c.854+2T>A
  • NM_001195803.2:c.977+2T>A
  • LRG_274t1:c.1358+2T>A
  • LRG_274:g.29071T>A
  • NC_000019.9:g.11224127T>A
  • NM_000527.4:c.1358+2T>A
  • c.1358+2T>A
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000544; dbSNP: rs193922567
NCBI 1000 Genomes Browser:
rs193922567
Molecular consequence:
  • NM_000527.5:c.1358+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195798.2:c.1358+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195799.2:c.1235+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195800.2:c.854+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195803.2:c.977+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002693161Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Sep 9, 2022) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Mutations in the low-density-lipoprotein receptor gene in German patients with familial hypercholesterolaemia.

Weiss N, Binder G, Keller C.

J Inherit Metab Dis. 2000 Dec;23(8):778-90.

PubMed [citation]
PMID:
11196104

Details of each submission

From Ambry Genetics, SCV002693161.2

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

Description

The c.1358+2T>A intronic pathogenic mutation results from a T to A substitution two nucleotides after coding exon 9 in the LDLR gene. The mutation was detected in a patient diagnosed with familial hypercholesterolemia (FH) and in individuals from FH cohorts (Weiss N et al., J. Inherit. Metab. Dis. 2000 Dec; 23(8):778-90; Fouchier SW et al. Hum Mutat. 2005 Dec;26(6):550-6; Tichý L et al. Atherosclerosis. 2012 Aug;223(2):401-8). 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 will 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: Nov 10, 2024