PhenoModifier-Variant Detail

Variant "MC1R:c.248C>T(p.Ser83Leu)"

Search result: 1 record

Variant information

Gene:

MC1R

Variant:

MC1R:c.248C>T(p.Ser83Leu)

Genomic location:

chr16:89985914(hg19)

HGVS:

SO Term	RefSeq
protein_coding	NM_002386.3:c.248C>T(p.Ser83Leu)
protein_coding	NM_006086.3:c.-3896C>T
protein_coding	NM_001197181.1:c.-14012C>T

dbSNP ID:

rs777024553

GWAS trait:

no data

Modifier statisitcs

Record:

1

Disorder:

1

Reference:

1

Effect type:

Penetrance(1)

Modifier effect:

Altered incidence(1)

Detail：

Target disease:

Melanoma (DOID_1909)

Effect type:

Penetrance

Modifier effect:

Altered incidence

Evidence:

Pooled RHC variants increased also significantly CDKN2A penetrance (OR=2.30; 95% CI 1.15-4.59; P=0.02).

Effect:

Melanocortin-1 receptor (MC1R) gene variants and dysplastic nevi modify penetrance of CDKN2A mutations in French melanoma-prone pedigrees

Reference:

PMID16214921

Title:

Melanocortin-1 receptor (MC1R) gene variants and dysplastic nevi modify penetrance of CDKN2A mutations in French melanoma-prone pedigrees.

Species studied:

Human

Abstract:

Germline mutations in CDKN2A gene predispose to melanoma with high but incomplete penetrance. Penetrance of CDKN2A gene was found to be significantly influenced by host factors (nevus phenotypes and sunburn) on one hand and by variants of MC1R gene (RHC variants consistently associated with red hair and fair skin) on the other hand. Our goal was to examine the joint effects of MC1R variants and other potential risk factors [total nevi, dysplastic nevi, pigmentary traits (skin, hair and eye color), skin reactions to sunlight, and degree of sun exposure] on CDKN2A penetrance. Clinical, genetic, and covariate data were recorded in 20 French melanoma-prone families with cosegregating CDKN2A mutations. Analysis of the cotransmission of melanoma and CDKN2A mutations was conducted by likelihood-based methods using the regressive logistic models, which can account for a variation of disease risk with age and can include the aforementioned risk factors as covariates. RHC variants, considered either alone or in the presence of pigmentation and nevus phenotypes, were found to increase significantly CDKN2A penetrance. Multivariate analysis, using a stepwise selection procedure, showed significant effects of two factors on melanoma risk in CDKN2A mutations carriers: RHC variants [odds ratio of hazard function (OR), 2.21; P = 0.03] and dysplastic nevi (OR, 2.93; P < 0.01). Such results may have important consequences to improve the prediction of melanoma risk in families.