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NM_000527.5(LDLR):c.1061-2A>G AND Familial hypercholesterolemia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 24, 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:
RCV001854899.13

Allele description [Variation Report for NM_000527.5(LDLR):c.1061-2A>G]

NM_000527.5(LDLR):c.1061-2A>G

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.1061-2A>G
HGVS:
  • NC_000019.10:g.11111512A>G
  • NG_009060.1:g.27132A>G
  • NM_000527.5:c.1061-2A>GMANE SELECT
  • NM_001195798.2:c.1061-2A>G
  • NM_001195799.2:c.938-2A>G
  • NM_001195800.2:c.557-2A>G
  • NM_001195803.2:c.680-2A>G
  • LRG_274:g.27132A>G
  • NC_000019.9:g.11222188A>G
  • c.1061-2A>G
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001009; dbSNP: rs879254773
NCBI 1000 Genomes Browser:
rs879254773
Molecular consequence:
  • NM_000527.5:c.1061-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001195798.2:c.1061-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001195799.2:c.938-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001195800.2:c.557-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001195803.2:c.680-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002246368Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 24, 2021) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Molecular spectrum of autosomal dominant hypercholesterolemia in France.

Marduel M, Carrié A, Sassolas A, Devillers M, Carreau V, Di Filippo M, Erlich D, Abifadel M, Marques-Pinheiro A, Munnich A, Junien C; French ADH Research Network., Boileau C, Varret M, Rabès JP.

Hum Mutat. 2010 Nov;31(11):E1811-24. doi: 10.1002/humu.21348.

PubMed [citation]
PMID:
20809525
PMCID:
PMC3152176
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002246368.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change affects an acceptor splice site in intron 7 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). This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with familial hypercholesterolemia (PMID: 11472756, 17539906). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 251632). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 26, 2024