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NM_000527.5(LDLR):c.82G>A (p.Glu28Lys) AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (4 submissions)
Last evaluated:
Oct 28, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV000495866.8

Allele description [Variation Report for NM_000527.5(LDLR):c.82G>A (p.Glu28Lys)]

NM_000527.5(LDLR):c.82G>A (p.Glu28Lys)

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.82G>A (p.Glu28Lys)
Other names:
NM_000527.5(LDLR):c.82G>A; p.Glu28Lys
HGVS:
  • NC_000019.10:g.11100237G>A
  • NG_009060.1:g.15857G>A
  • NM_000527.5:c.82G>AMANE SELECT
  • NM_001195798.2:c.82G>A
  • NM_001195799.2:c.82G>A
  • NM_001195800.2:c.82G>A
  • NM_001195803.2:c.82G>A
  • NP_000518.1:p.Glu28Lys
  • NP_000518.1:p.Glu28Lys
  • NP_001182727.1:p.Glu28Lys
  • NP_001182728.1:p.Glu28Lys
  • NP_001182729.1:p.Glu28Lys
  • NP_001182732.1:p.Glu28Lys
  • LRG_274t1:c.82G>A
  • LRG_274:g.15857G>A
  • LRG_274p1:p.Glu28Lys
  • NC_000019.9:g.11210913G>A
  • NM_000527.4:c.82G>A
Protein change:
E28K
Links:
dbSNP: rs551747280
NCBI 1000 Genomes Browser:
rs551747280
Molecular consequence:
  • NM_000527.5:c.82G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.82G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.82G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.82G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.82G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hypercholesterolemia, familial, 1
Synonyms:
LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000583628U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Mar 30, 2017) 		germlineclinical testing

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

SCV000606008Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum
no assertion criteria provided
Pathogenicgermlineresearch

SCV002817164ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)		Uncertain significance
(Oct 28, 2022) 		germlinecuration

Citation Link,

SCV003925258New York Genome Center
criteria provided, single submitter

(NYGC Assertion Criteria 2020)		Uncertain significance
(Aug 3, 2022) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes11not providednot providednot providedclinical testing
not providedgermlineunknown1not providednot provided1not providedresearch, curation, clinical 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 U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille, SCV000583628.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Dutch Lipid Clinic Scoring : Probable FH

Description

ACMG Guidelines: Pathogenic (i)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not provided1not provided

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000606008.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel, SCV002817164.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000527.5(LDLR):c.82G>A (p.Glu28Lys) variant is classified as a variant of uncertain significance for Familial Hypercholesterolemia by applying evidence code BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: BP4_Met : REVEL = 0.306. It is below 0.50. splicing evaluation is required. A) not on limits B) does not create AG C) there is a AG nearby The variant does not alter splicing

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

From New York Genome Center, SCV003925258.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024