|(G;T)||7||~8 fold increase in relative risk for breast cancer|
|(T;T)||0||common in complete genomics|
rs28904921, also known as c.7271T>G, p.Val2424Gly and V2424G, is a mutation in the ATM gene on chromosome 11.
Although most high risk (causative) mutations for cancers prematurely truncate encoded proteins [PMID 26014596], the rs28904921(G) mutation is a missense variant that appears to lead to a quite high relative risk for breast cancer (relative risk increase of 8.0, CI: 2.8 to 22.5, p=0.0005). In contrast to most BRCA mutations, which are considered tumor suppressors and functionally recessive, this ATM mutation is considered a dominant negative, since loss of the wild-type allele in tumors with the ATM mutation is not consistently observed.[PMID 21787400]
Note that the confidence intervals are quite large, so although the relative risk is calculated as increasing eight-fold, the authors cited indicate that they can only state with 95% confidence that the "true" increase in relative risk lies somewhere between 2.8 and 22.5.
Somewhat similarly, a 2016 publication study involving 42,000 breast cancer cases concluded that rs28904921(G) carriers had an odds ratio of 11 (CI:1.4-85; p=0.0012) and a 52% (CI: 28-80%) chance of developing the disease by age 70.10.1136/jmedgenet-2016-103839
|Disease||Ataxia-telangiectasia variant T-cell prolymphocytic leukemia Breast cancer Hereditary cancer-predisposing syndrome Ataxia-telangiectasia syndrome not provided|
|CLNDBN||Ataxia-telangiectasia variant T-cell prolymphocytic leukemia Breast cancer, susceptibility to Hereditary cancer-predisposing syndrome Ataxia-telangiectasia syndrome not provided|
|CLNSRC||Inc. OMIM Allelic Variant UniProtKB (protein)|
|CLNACC||RCV000003159.5, RCV000003160.7, RCV000003161.5, RCV000115244.7, RCV000168223.5, RCV000212060.2,|