NM_053056.2(CCND1):c.723G>A (p.Pro241=) AND VON HIPPEL-LINDAU SYNDROME, MODIFIER OF

Clinical significance:risk factor (Last evaluated: May 1, 2013)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000087019.6

Allele description [Variation Report for NM_053056.2(CCND1):c.723G>A (p.Pro241=)]

NM_053056.2(CCND1):c.723G>A (p.Pro241=)

Gene:
CCND1:cyclin D1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.3
Genomic location:
Preferred name:
NM_053056.2(CCND1):c.723G>A (p.Pro241=)
HGVS:
  • NC_000011.10:g.69648142G>A
  • NG_007375.1:g.12038G>A
  • NM_053056.2:c.723G>A
  • NP_444284.1:p.Pro241=
  • LRG_990t1:c.723G>A
  • LRG_990:g.12038G>A
  • LRG_990p1:p.Pro241=
  • NC_000011.9:g.69462910G>A
Links:
OMIM: 168461.0001; dbSNP: rs9344
NCBI 1000 Genomes Browser:
rs9344
Molecular consequence:
  • NM_053056.2:c.723G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
VON HIPPEL-LINDAU SYNDROME, MODIFIER OF
Identifiers:

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000119833OMIMno assertion criteria providedrisk factor
(May 1, 2013)
germlineliterature only

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Effects of cyclin D1 polymorphism on age of onset of hereditary nonpolyposis colorectal cancer.

Kong S, Amos CI, Luthra R, Lynch PM, Levin B, Frazier ML.

Cancer Res. 2000 Jan 15;60(2):249-52.

PubMed [citation]
PMID:
10667569

Cyclin D1 polymorphism and increased risk of colorectal cancer at young age.

Kong S, Wei Q, Amos CI, Lynch PM, Levin B, Zong J, Frazier ML.

J Natl Cancer Inst. 2001 Jul 18;93(14):1106-8. No abstract available.

PubMed [citation]
PMID:
11459873
See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000119833.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (5)

Description

Susceptibility to Colorectal Cancer

The CCND1 gene contains a common G/A polymorphism at nucleotide 870 (codon 242) that modulates mRNA splicing to produce 2 transcripts, one of which lacks the exon 5 sequence encoding a protein-destabilizing (PEST) destruction box responsible for rapid turnover of the protein. Both the A and G alleles of the polymorphism encode the 2 transcripts, but the A allele preferentially encodes the transcript lacking exon 5, leading to a state of increased CCND1 level, even in the heterozygous state. The CCND1 870G-A polymorphism influences susceptibility to colorectal cancer (114500) (Kong et al., 2000; Kong et al., 2001). Le Marchand et al. (2003) found an association between the CCND1 870A allele and advanced colorectal cancer (114500) in white and Hawaiian but not Japanese patients; the association was stronger for rectal than colon cancer.

von Hippel-Lindau Syndrome, Modifier of

To assess the influence of variation in CCND1 on the retinal, renal, and central nervous system (CNS) manifestations of von Hippel-Lindau disease (193300), Zatyka et al. (2002) genotyped 118 patients for the codon 242 SNP. Thirty patients (25%) possessed the AA genotype, 56 (47%) the AG genotype, and 32 (27%) the GG genotype. The number of retinal angiomas was significantly higher in individuals harboring the G allele compared with AA homozygotes (p of 0.04). Possession of 1 or more G alleles was associated with earlier diagnosis of CNS hemangioblastoma by almost 2-fold, although the difference did not attain statistical significance (p of 0.05). A similar analysis for onset of renal cell carcinoma showed no evidence of an association with CCND1 genotype.

Susceptibility to Multiple Myeloma, t(11;14) Type

Weinhold et al. (2013) performed a metaanalysis of 2 genomewide association studies of multiple myeloma (254500), including a total of 1,661 affected individuals, to investigate the risk for developing a specific tumor karyotype. They found that the t(11;14)(q13;q32) translocation, in which CCND1 is placed under the control of the immunoglobulin heavy chain (147100) enhancer, was strongly associated with the CCND1 870A-G polymorphism (rs603965) (p = 7.96 x 10(-11)). While the majority of studies had found an association between the 870A allele, which allows for the production of the cyclin D1b transcript, and increased cancer risk, Weinhold et al. (2013) found association between the 870G allele, which results in production of the D1a transcript, and risk of t(11;14) multiple myeloma. The lack of an association of CCND1 genotype with other subgroups of multiple myeloma, which are also characterized by immunoglobulin translocations deregulating other genes, argues against the rs603965 genotype facilitating the development through a general mechanism. Weinhold et al. (2013) concluded that these results provided a model in which a constitutive genetic factor is associated with risk of a specific chromosomal translocation.

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

Last Updated: Mar 30, 2019

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