rs36053993

badMag 8.5

This is a variant in the MUTYH gene that changes a glycine to an aspartate.

Key Literature Trait Associations

MUTYH-Associated Polyposis and Colorectal Cancer

The MUTYH G396D variant (c.1187G>A, p.Gly396Asp) is the second most common MUTYH pathogenic variant in Northern Europeans. Like Y179C, it disrupts base excision repair. Compound heterozygous individuals carrying one G396D and one Y179C have a greater than 20-fold elevated colorectal cancer risk. Monoallelic carriers have a modest and contested increased risk. Biallelic carriers require intensive colonoscopy surveillance beginning in late teens.

Theodoratou E et al. “A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants.” British Journal of Cancer (2010)
Allele T
OR 6.47
p —
N 36,089
Meta-analysis
multi-ancestry
Varela I et al. “Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.” Nature 469(7331):539-542 (2011)
Allele T
OR 1.35
p 5.0e-3
Meta-analysis
Laskar RS et al. “Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.” Annals of Oncology : Official Journal of the European Society for Medical Oncology 35(6):523-536 (2024)
Allele T
OR 1.80
p —
N 72,005
Preliminary work
multi-ancestry

Prostate cancer

A germline sequencing study of two hereditary prostate cancer cohorts (n=1,963) found rs36053993 in MUTYH to be nominally associated with prostate cancer risk in the North American dataset (p=0.031). No odds ratio or confidence interval was reported, and the association was not replicated in the second cohort. Carriers showed no evidence of younger age at diagnosis or higher-grade disease. This represents preliminary evidence only; the association has not been confirmed in larger independent studies.

Foley GR et al. “Germline Sequencing of DNA Damage Repair Genes in Two Hereditary Prostate Cancer Cohorts Reveals New Disease Risk-Associated Gene Variants.” Cancers (2024)
Allele T
OR —
p 3.1e-2
N 1,963
Preliminary work
European
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ClinVar annotation

Pathogenic★★★☆
77 submitters76 publications

Familial adenomatous polyposis 2; Endometrial cancer; not provided; not specified; Carcinoma of colon; Hereditary cancer-predisposing syndrome; Colorectal adenomatous polyposis, autosomal recessive, with pilomatricomas; Neoplasm of stomach;Familial adenomatous polyposis 2; Small intestine carcinoid; Pilomatrixoma;Neoplasm of stomach;Familial adenomatous polyposis 2; Ovarian carcinoma; Breast carcinoma; Colon cancer; Familial colorectal cancer; MUTYH-related disorder; Diffuse midline glioma, H3 K27-altered; Inherited polyposis and early onset colorectal cancer - germline testing; Familial adenomatous polyposis 2;Gastric cancer; Pleomorphic xanthoastrocytoma BRAF mutant; Infant-type hemispheric glioma; Pilocytic astrocytoma; Ependymoma

View on ClinVar →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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rs36053993 (MUTYH) — genewizard.net