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NM_000527.5(LDLR):c.1845+11C>G AND Familial hypercholesterolemia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 2, 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:
RCV001853403.6

Allele description [Variation Report for NM_000527.5(LDLR):c.1845+11C>G]

NM_000527.5(LDLR):c.1845+11C>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.1845+11C>G
HGVS:
  • NC_000019.10:g.11117009C>G
  • NG_009060.1:g.32629C>G
  • NM_000527.5:c.1845+11C>GMANE SELECT
  • NM_001195798.2:c.1845+11C>G
  • NM_001195799.2:c.1722+11C>G
  • NM_001195800.2:c.1341+11C>G
  • NM_001195803.2:c.1464+11C>G
  • LRG_274t1:c.1845+11C>G
  • LRG_274:g.32629C>G
  • NC_000019.9:g.11227685C>G
  • NM_000527.4:c.1845+11C>G
  • c.1845+11C>G
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001160; dbSNP: rs370245937
NCBI 1000 Genomes Browser:
rs370245937
Molecular consequence:
  • NM_000527.5:c.1845+11C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195798.2:c.1845+11C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195799.2:c.1722+11C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195800.2:c.1341+11C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.1464+11C>G - intron variant - [Sequence Ontology: SO:0001627]

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
SCV002116503Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 2, 2021) 		germlineclinical testing

PubMed (2)
[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

Genetic screening protocol for familial hypercholesterolemia which includes splicing defects gives an improved mutation detection rate.

Graham CA, McIlhatton BP, Kirk CW, Beattie ED, Lyttle K, Hart P, Neely RD, Young IS, Nicholls DP.

Atherosclerosis. 2005 Oct;182(2):331-40.

PubMed [citation]
PMID:
16159606

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002116503.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant is associated with activation of a cryptic splice site in intron 12, which introduces a premature termination codon (PMID: 16159606). The resulting mRNA is expected to undergo nonsense-mediated decay. This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 16159606). ClinVar contains an entry for this variant (Variation ID: 226375). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 12 of the LDLR gene. It does not directly change the encoded amino acid sequence of the LDLR protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product.

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

Last Updated: Sep 29, 2024