NM_000527.5(LDLR):c.1056C>T (p.Cys352=) AND not specified

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Mar 11, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000780374.5

Allele description [Variation Report for NM_000527.5(LDLR):c.1056C>T (p.Cys352=)]

NM_000527.5(LDLR):c.1056C>T (p.Cys352=)

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.1056C>T (p.Cys352=)

HGVS:

NC_000019.10:g.11110767C>T
NG_009060.1:g.26387C>T
NM_000527.5:c.1056C>TMANE SELECT
NM_001195798.2:c.1056C>T
NM_001195799.2:c.933C>T
NM_001195800.2:c.552C>T
NM_001195803.2:c.675C>T
NP_000518.1:p.Cys352=
NP_000518.1:p.Cys352=
NP_001182727.1:p.Cys352=
NP_001182728.1:p.Cys311=
NP_001182729.1:p.Cys184=
NP_001182732.1:p.Cys225=
LRG_274t1:c.1056C>T
LRG_274:g.26387C>T
LRG_274p1:p.Cys352=
NC_000019.9:g.11221443C>T
NM_000527.4:c.1056C>T

Links:

dbSNP: rs13306515

NCBI 1000 Genomes Browser:

rs13306515

Molecular consequence:

NM_000527.5:c.1056C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001195798.2:c.1056C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001195799.2:c.933C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001195800.2:c.552C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001195803.2:c.675C>T - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV000917576	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Sep 22, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002064929	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Mar 11, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000917576

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(Sep 22, 2017)

germline

clinical testing

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

Citation Link,

SCV002064929

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Mar 11, 2019)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Array-based resequencing for mutations causing familial hypercholesterolemia.

Chiou KR, Charng MJ, Chang HM.

Atherosclerosis. 2011 Jun;216(2):383-9. doi: 10.1016/j.atherosclerosis.2011.02.006. Epub 2011 Mar 3.

PubMed [citation]

PMID:: 21376320

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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917576.1

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

Description

Variant summary: The LDLR c.1056C>T (p.Cys352Cys) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in 222/276416 control chromosomes from all ethnicities, but was observed predominantly in the East Asian subpopulation at a frequency of 0.008694 (164/18864). This frequency is about 7 times the estimated maximal expected allele frequency of a pathogenic LDLR variant (0.0012508), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. The variant has been identified in patients reported in the literature without strong evidence for causality. In addition, the variant has been found to co-occur with a pathogenic LDLR mutation in a patient (c.259G>T/p.W66G), supporting a benign outcome for the variant of interest (Jensen_1996). One clinical diagnostic laboratory has classified this variant as benign. Taken together, this variant is classified as likely benign, until additional studies become available (ie, clinical and/or functional studies).

#	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

From Genetic Services Laboratory, University of Chicago, SCV002064929.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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