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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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000917576Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely benign
(Sep 22, 2017) 		germlineclinical testing

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

Citation Link,

SCV002064929Genetic Services Laboratory, University of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely benign
(Mar 11, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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).

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

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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024