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NM_000527.5(LDLR):c.313+1_313+2dup AND Familial hypercholesterolemia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 21, 2020
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:
RCV001306671.5

Allele description [Variation Report for NM_000527.5(LDLR):c.313+1_313+2dup]

NM_000527.5(LDLR):c.313+1_313+2dup

Gene:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.5(LDLR):c.313+1_313+2dup
HGVS:
  • NC_000019.10:g.11102787_11102788dup
  • NG_009060.1:g.18407_18408dup
  • NM_000527.5:c.313+1_313+2dupMANE SELECT
  • NM_001195798.2:c.313+1_313+2dup
  • NM_001195799.2:c.191-2433_191-2432dup
  • NM_001195800.2:c.313+1_313+2dup
  • NM_001195803.2:c.313+1_313+2dup
  • LRG_274:g.18407_18408dup
  • NC_000019.9:g.11213462_11213463insGT
  • NC_000019.9:g.11213463_11213464dup
Links:
dbSNP: rs2077233623
NCBI 1000 Genomes Browser:
rs2077233623
Molecular consequence:
  • NM_001195799.2:c.191-2433_191-2432dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.313+1_313+2dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195798.2:c.313+1_313+2dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195800.2:c.313+1_313+2dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195803.2:c.313+1_313+2dup - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV001496052Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 21, 2020) 		germlineclinical testing

PubMed (3)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001496052.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant has not been reported in the literature in individuals with LDLR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 3 of the LDLR gene. It does not directly change the encoded amino acid sequence of the LDLR protein, but it affects a nucleotide within the consensus splice site of the intron. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.

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

Last Updated: Sep 29, 2024