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

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Apr 29, 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:
RCV000237142.5

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

NM_000527.5(LDLR):c.4G>C (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>C (p.Gly2Arg)
Other names:
NM_000527.5(LDLR):c.4G>C
HGVS:
  • NC_000019.10:g.11089552G>C
  • NG_009060.1:g.5172G>C
  • NM_000527.5:c.4G>CMANE SELECT
  • NM_001195798.2:c.4G>C
  • NM_001195799.2:c.4G>C
  • NM_001195800.2:c.4G>C
  • NM_001195803.2:c.4G>C
  • 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>C
  • LRG_274:g.5172G>C
  • LRG_274p1:p.Gly2Arg
  • NC_000019.9:g.11200228G>C
  • NM_000527.4:c.4G>C
  • NR_163945.1:n.108C>G
  • P01130:p.Gly2Arg
  • c.4G>C
Protein change:
G2R
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001001; UniProtKB: P01130#VAR_011862
Molecular consequence:
  • NM_000527.5:c.4G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.4G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.4G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.4G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.4G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_163945.1:n.108C>G - 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
SCV000294410LDLR-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,

SCV000588479Laboratory of Genetics and Molecular Cardiology, University of São Paulo - HipercolBrasil
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 1, 2016) 		germlineresearch

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

SCV002817168ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)		Uncertain significance
(Apr 29, 2022) 		germlinecuration

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Molecular basis of familial hypercholesterolemia in Brazil: Identification of seven novel LDLR gene mutations.

Salazar LA, Hirata MH, Cavalli SA, Nakandakare ER, Forti N, Diament J, Giannini SD, Bertolami MC, Hirata RD.

Hum Mutat. 2002 Apr;19(4):462-3.

PubMed [citation]
PMID:
11933210

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 LDLR-LOVD, British Heart Foundation, SCV000294410.2

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

From Laboratory of Genetics and Molecular Cardiology, University of São Paulo - HipercolBrasil, SCV000588479.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)

Description

%MAF(ExAC):0.001731

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

From ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel, SCV002817168.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM_000527.5(LDLR):c.4G>C (p.Gly2Arg)variant is classified as uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence code PM2 and PP4 as defined by the ClinGen Familial NM_000527.5(LDLR):c.4G>C (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 - PopMax MAF = 0.00016 (0.016%) in African exomes (gnomAD v2.1.1). PP4 - Variant meets PM2 and is identified in one index cases who fulfills SB criteria for FH (1 case from CGMC, UFGOD (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière)).

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

Last Updated: Sep 29, 2024