U.S. flag

An official website of the United States government

NM_000527.5(LDLR):c.1845+2del AND Homozygous familial hypercholesterolemia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 16, 2019
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:
RCV004017989.1

Allele description [Variation Report for NM_000527.5(LDLR):c.1845+2del]

NM_000527.5(LDLR):c.1845+2del

Gene:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.5(LDLR):c.1845+2del
HGVS:
  • NC_000019.10:g.11117000del
  • NG_009060.1:g.32620del
  • NM_000527.5:c.1845+2delMANE SELECT
  • NM_001195798.2:c.1845+2del
  • NM_001195799.2:c.1722+2del
  • NM_001195800.2:c.1341+2del
  • NM_001195803.2:c.1464+2del
  • LRG_274:g.32620del
  • NC_000019.10:g.11117000delT
  • NC_000019.9:g.11227676del
Molecular consequence:
  • NM_000527.5:c.1845+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195798.2:c.1845+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195799.2:c.1722+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195800.2:c.1341+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195803.2:c.1464+2del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Homozygous familial hypercholesterolemia
Synonyms:
Familial hypercholesterolemia - homozygous
Identifiers:
MONDO: MONDO:0018328; MedGen: C0342881

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
SCV004847629Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely Pathogenic
(Apr 16, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847629.1

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

Description

The c.1845+2delT variant in LDLR has not been previously reported in individuals with familial hypercholesterolemia (FH) but has been identified in 0.003% (1/30616) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is a deletion of one nucleotide that occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the LDLR gene is an established disease mechanism in autosomal dominant FH. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant FH. ACMG/AMP Criteria applied: PVS1, PM2.

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

Last Updated: May 7, 2024