NM_000527.5(LDLR):c.2289G>T (p.Glu763Asp) AND not specified

Germline classification:: Likely benign (1 submission)
Last evaluated:: Dec 4, 2017
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:: RCV004017509.1

Allele description [Variation Report for NM_000527.5(LDLR):c.2289G>T (p.Glu763Asp)]

NM_000527.5(LDLR):c.2289G>T (p.Glu763Asp)

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.2289G>T (p.Glu763Asp)

HGVS:

NC_000019.10:g.11123322G>T
NG_009060.1:g.38942G>T
NM_000527.5:c.2289G>TMANE SELECT
NM_001195798.2:c.2289G>T
NM_001195799.2:c.2166G>T
NM_001195800.2:c.1785G>T
NM_001195803.2:c.1755G>T
NP_000518.1:p.Glu763Asp
NP_000518.1:p.Glu763Asp
NP_001182727.1:p.Glu763Asp
NP_001182728.1:p.Glu722Asp
NP_001182729.1:p.Glu595Asp
NP_001182732.1:p.Glu585Asp
LRG_274t1:c.2289G>T
LRG_274:g.38942G>T
LRG_274p1:p.Glu763Asp
NC_000019.9:g.11233998G>T
NM_000527.4:c.2289G>T
c.2289G>T

Protein change:

E585D

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001621; dbSNP: rs774698247

NCBI 1000 Genomes Browser:

rs774698247

Molecular consequence:

NM_000527.5:c.2289G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.2289G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.2166G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1785G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1755G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004848151	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Benign (Dec 4, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25057385, 22883975, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004848151

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Benign
(Dec 4, 2017)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel low density lipoprotein receptor variant linked to early onset acute myocardial infarction in a patient with familial hypercholesterolaemia.

Bangash FA, Antbring CR, Wald DS.

JRSM Open. 2014 Apr;5(4):2042533313518917. doi: 10.1177/2042533313518917.

PubMed [citation]

PMID:: 25057385
PMCID:: PMC4012663

Genetic analysis of familial hypercholesterolaemia in Western Australia.

Hooper AJ, Nguyen LT, Burnett JR, Bates TR, Bell DA, Redgrave TG, Watts GF, van Bockxmeer FM.

Atherosclerosis. 2012 Oct;224(2):430-4. doi: 10.1016/j.atherosclerosis.2012.07.030. Epub 2012 Jul 27.

PubMed [citation]

PMID:: 22883975

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848151.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.Glu763Asp variant in LDLR has been reported in 2 individuals with hypercholesterolemia (Hooper 2012, Bangash 2014). This variant has been identified in 0.21% (66/30782) of South Asian chromosomes, including 3 homozygotes, by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs774698247) and is reported in ClinVar (Variation ID: 226389). Computational prediction tools and conservation analysis suggest that the p.Glu763Asp variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the p.Glu763Asp variant is likely benign due to its frequency in the general population. ACMG/AMP Criteria applied: PS4_Supporting, BP4, BS1.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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