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NM_000527.5(LDLR):c.4G>A (p.Gly2Arg) AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Mar 8, 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:
RCV000238070.5

Allele description [Variation Report for NM_000527.5(LDLR):c.4G>A (p.Gly2Arg)]

NM_000527.5(LDLR):c.4G>A (p.Gly2Arg)

Genes:
LDLR-AS1:LDLR antisense RNA 1 [Gene - HGNC]
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.4G>A (p.Gly2Arg)
Other names:
NM_000527.5(LDLR):c.4G>A
HGVS:
  • NC_000019.10:g.11089552G>A
  • NG_009060.1:g.5172G>A
  • NM_000527.5:c.4G>AMANE SELECT
  • NM_001195798.2:c.4G>A
  • NM_001195799.2:c.4G>A
  • NM_001195800.2:c.4G>A
  • NM_001195803.2:c.4G>A
  • NP_000518.1:p.Gly2Arg
  • NP_000518.1:p.Gly2Arg
  • NP_001182727.1:p.Gly2Arg
  • NP_001182728.1:p.Gly2Arg
  • NP_001182729.1:p.Gly2Arg
  • NP_001182732.1:p.Gly2Arg
  • LRG_274t1:c.4G>A
  • LRG_274:g.5172G>A
  • LRG_274p1:p.Gly2Arg
  • NC_000019.9:g.11200228G>A
  • NM_000527.4:c.4G>A
  • NR_163945.1:n.108C>T
  • P01130:p.Gly2Arg
  • c.4G>A
Protein change:
G2R
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001027; UniProtKB: P01130#VAR_011862; dbSNP: rs5931
NCBI 1000 Genomes Browser:
rs5931
Molecular consequence:
  • NM_000527.5:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_163945.1:n.108C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000294409LDLR-LOVD, British Heart Foundation
criteria provided, single submitter

(ACGS Guidelines, 2013)		Likely benign
(Mar 25, 2016) 		germlineliterature only

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

Citation Link,

SCV000605994Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum
no assertion criteria provided
Pathogenicgermlineresearch

SCV002506406ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)		Uncertain significance
(Mar 8, 2022) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedresearch, curation
not providedgermlineyes1not providednot provided1not providedliterature only

Citations

PubMed

Update of the molecular basis of familial hypercholesterolemia in The Netherlands.

Fouchier SW, Kastelein JJ, Defesche JC.

Hum Mutat. 2005 Dec;26(6):550-6.

PubMed [citation]
PMID:
16250003

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000294409.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000605994.1

#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, SCV002506406.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM_000527.5(LDLR):c.4G>A (p.Gly2Arg) variant is classified as uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence code PM2 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: PM2 - Variant is absent from gnomAD (gnomAD v2.1.1).

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

Last Updated: Aug 5, 2023