rs28904921
| Orientation | plus |
| Stabilized | plus |
| Geno | Mag | Summary |
|---|---|---|
| (G;T) | 7 | ~8 fold increase in relative risk for breast cancer |
| (T;T) | 0 | common in complete genomics |
| Make rs28904921(G;G) |
| Reference | GRCh38 38.1/141 |
| Chromosome | 11 |
| Position | 108329202 |
| Gene | ATM, C11orf65 |
| is a | snp |
| is | mentioned by |
| dbSNP | rs28904921 |
| dbSNP (classic) | rs28904921 |
| ClinGen | rs28904921 |
| ebi | rs28904921 |
| HLI | rs28904921 |
| Exac | rs28904921 |
| Gnomad | rs28904921 |
| Varsome | rs28904921 |
| LitVar | rs28904921 |
| Map | rs28904921 |
| PheGenI | rs28904921 |
| Biobank | rs28904921 |
| 1000 genomes | rs28904921 |
| hgdp | rs28904921 |
| ensembl | rs28904921 |
| geneview | rs28904921 |
| scholar | rs28904921 |
| rs28904921 | |
| pharmgkb | rs28904921 |
| gwascentral | rs28904921 |
| openSNP | rs28904921 |
| 23andMe | rs28904921 |
| SNPshot | rs28904921 |
| SNPdbe | rs28904921 |
| MSV3d | rs28904921 |
| GWAS Ctlg | rs28904921 |
| Max Magnitude | 7 |
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
| ClinVar | |
|---|---|
| Risk | rs28904921(G;G) |
| Alt | rs28904921(G;G) |
| Reference | Rs28904921(T;T) |
| Significance | Other |
| Disease | Ataxia-telangiectasia variant T-cell prolymphocytic leukemia Breast cancer Hereditary cancer-predisposing syndrome Ataxia-telangiectasia syndrome not provided Neoplasm of breast |
| Variation | info |
| Gene | C11orf65 ATM |
| CLNDBN | Ataxia-telangiectasia variant T-cell prolymphocytic leukemia Breast cancer, susceptibility to Hereditary cancer-predisposing syndrome Ataxia-telangiectasia syndrome not provided Neoplasm of breast |
| Reversed | 0 |
| HGVS | NC_000011.9:g.108199929T>G |
| CLNSRC | OMIM Allelic Variant UniProtKB (protein) |
| CLNACC | RCV000003159.5, RCV000003160.7, RCV000003161.5, RCV000115244.8, RCV000168223.6, RCV000212060.3, RCV000417259.1, |
