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NM_000527.5(LDLR):c.139G>C (p.Asp47His) AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 13, 2021
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:
RCV000508959.4

Allele description [Variation Report for NM_000527.5(LDLR):c.139G>C (p.Asp47His)]

NM_000527.5(LDLR):c.139G>C (p.Asp47His)

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.139G>C (p.Asp47His)
Other names:
NM_000527.5(LDLR):c.139G>C; p.Asp47His
HGVS:
  • NC_000019.10:g.11100294G>C
  • NG_009060.1:g.15914G>C
  • NM_000527.5:c.139G>CMANE SELECT
  • NM_001195798.2:c.139G>C
  • NM_001195799.2:c.139G>C
  • NM_001195800.2:c.139G>C
  • NM_001195803.2:c.139G>C
  • NP_000518.1:p.Asp47His
  • NP_000518.1:p.Asp47His
  • NP_001182727.1:p.Asp47His
  • NP_001182728.1:p.Asp47His
  • NP_001182729.1:p.Asp47His
  • NP_001182732.1:p.Asp47His
  • LRG_274t1:c.139G>C
  • LRG_274:g.15914G>C
  • LRG_274p1:p.Asp47His
  • NC_000019.9:g.11210970G>C
  • NM_000527.4:c.139G>C
Protein change:
D47H
Links:
dbSNP: rs778284147
NCBI 1000 Genomes Browser:
rs778284147
Molecular consequence:
  • NM_000527.5:c.139G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.139G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.139G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.139G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.139G>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000606025Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum
no assertion criteria provided
Pathogenicgermlineresearch

SCV002506332ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)		Uncertain significance
(Dec 13, 2021) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedresearch, curation

Details of each submission

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000606025.1

#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, SCV002506332.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000527.5(LDLR):c.139G>C (p.Asp47His) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2 and PP3) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755 The supporting evidence is as follows: PM2 - This variant is absent from gnomAD (gnomAD v2.1.1). PP3 - REVEL = 0.977. It is above 0.75, so met.

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

Last Updated: Aug 5, 2023