ATM
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
ATM (HGNC:795) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
ATM serine/threonine kinase
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
ATA, ATDC, ATC, ATD
Alias symbols
TEL1, TELO1
%HI
0.97(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
0.85(Read more about gnomAD LOEUF score)
Cytoband
11q22.3
Genomic Coordinates
GRCh37/hg19: chr11:108093794-108239829 NCBI Ensembl UCSC
GRCh38/hg38: chr11:108223067-108369102 NCBI Ensembl UCSC
MANE Select Transcript
NM_000051.4 ENST00000675843.1 (Read more about MANE Select)
Function
Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor (PubMed:9733514, PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15456891, PubMed:15448695, PubMed:15916964, PubMed:17923702). Recognizes the substrate consensus sequence [ST]-Q (PubMed:9733514, PubMed:10550055, PubMed:10839545, PubMed:10... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-33098
ClinGen Curation ID:
CCID:006708
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
04/08/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Breast Cancer, Prostate Cancer Monarch
HI Evidence:
  • PUBMED: 3574400
    This study examined the cancer incidence of individuals with heterozygous pathogenic variants in over 120 families with ataxia telangiectasia (A-T). The cancer incidence in adult blood relatives of A-T individuals were compared to their adult spouses. The adjusted cancer rate ratio was 1.6 for males (P=0.032) and 2 for females (P=0.013) and a relative risk of 2.3 (p=0.014) for males and 3.1 (P=0.004). Breast cancer was the most common site with a relative risk of 6.8 (P=0.006).
  • PUBMED: 27595995
    The study examined the association of PALB2, CHEK2, and ATM with breast cancer. The p.Val2424Gly variant in the ATM gene was found to be associated with breast cancer with an OR of 11.6 (1.50 to 89.9) (p= 0.0012). This variant has been observed either as homozygous or compound heterozygous with another pathogenic variant in the gene in individuals with A-T (PMID: 9463314, 8755918). Furthermore, experimental studies have demonstrated that the variant leads to loss of kinase activity and therefore loss of function (PMID: 11382771, 11830610, 18634022, 19431188)
  • PUBMED: 15928302
    In a cohort of 1160 relatives in 132 families with at least one patient with A-T, and either a loss of function, in-frame, or a missense variant. Statistically significant association with female breast cancer was found among the heterozygous carriers (RR = 2.23, 95% CI = 1.16 to 4.28) when compared to the control cohort. The cumulative cancer risk among heterozygous of A-T carriers is 8.8% (95% CI = 3.5% to 21.4%) by age 50 years and 16.6% (95% CI = 9.1% to 29.3%) by age 80 years. There was no statistically significant difference in the cancer risks among individuals with different variant types.
HI Evidence Comments:
PMIDS: 11830610, 15928302, 16832357, 16958054, 21787400, 27595995, 22585167, 26098866, 26483394, 27433846, 27324988, 27989354

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000011.9) (NC_000011.10)