U.S. flag

An official website of the United States government

NM_000527.5(LDLR):c.2547+1G>T AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 12, 2014
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:
RCV002455811.2

Allele description [Variation Report for NM_000527.5(LDLR):c.2547+1G>T]

NM_000527.5(LDLR):c.2547+1G>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.2547+1G>T
HGVS:
  • NC_000019.10:g.11129671G>T
  • NG_009060.1:g.45291G>T
  • NM_000527.5:c.2547+1G>TMANE SELECT
  • NM_001195798.2:c.2547+1G>T
  • NM_001195799.2:c.2424+1G>T
  • NM_001195800.2:c.2043+1G>T
  • NM_001195803.2:c.2013+1G>T
  • LRG_274t1:c.2547+1G>T
  • LRG_274:g.45291G>T
  • NC_000019.9:g.11240347G>T
  • NM_000527.4:c.2547+1G>T
Molecular consequence:
  • NM_000527.5:c.2547+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195798.2:c.2547+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195799.2:c.2424+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195800.2:c.2043+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195803.2:c.2013+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002740118Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Aug 12, 2014) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Update of the Portuguese Familial Hypercholesterolaemia Study.

Medeiros AM, Alves AC, Francisco V, Bourbon M; investigators of the Portuguese FH Study..

Atherosclerosis. 2010 Oct;212(2):553-8. doi: 10.1016/j.atherosclerosis.2010.07.012. Epub 2010 Aug 8.

PubMed [citation]
PMID:
20828696

Details of each submission

From Ambry Genetics, SCV002740118.2

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

Description

The c.2547+1G>T intronic pathogenic mutation results from a G to T one nucleotide after coding exon 17 of the LDLR gene. A pathogenic mutation (c.2547+1G>A) at the same position has been reported in the literature; reportedly, this mutation resulted in skipping of exon 17 and the generation of an alternate stop codon (Medeiros AM et al. Atherosclerosis. 2010;212(2):553-8). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, the c.2547+1G>T alteration is predicted to abolish the native donor splice site; however, direct evidence is unavailable. In addition to the clinical data presented in the literature, since alterations that disrupt the canonical splice donor site are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

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

Last Updated: May 1, 2024