Genetic Information

Gene & Transcript Details

Gene
ATM
Transcript
NM_000051.3 MANE Select
Total Exons
—
Reference Sequence
NC_000011.9
Alternative Transcripts
IDStatusDetails
NM_000051.3 RefSeq Select 13147 nt | 386–9556
NM_000051.4 MANE Select 12915 nt | 151–9321

Variant Details

HGVS Notation
NM_000051.3:c.5681_5682del
Protein Change
E1894Afs*9
Location
Exon 38 (Exon 38 of )
38
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.0 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Unknown
0 publications
Clinical Statement

""

COSMIC Somatic Evidence

Open
COSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC Preview
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Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene ATM.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: ATME1894Afs*9ATME1894Afs*9SomaticNCBI Gene:472|Show additional gene information Variant OverviewATM, a kinase involved in the DNA damage response, is mutated in various solid and hematologic malignancies.The ATM E1894Afs*9 is a truncating mutation in a tumor suppressor gene, and therefore is likely oncogenic.Hide mutation effect description The mutation effect description for truncating mutations in ATM is: ATM truncating mutations can produce several forms of C-terminally truncated ATM proteins. When found in the germline, these mutations result in ataxia-telangiectasia syndrome, which increases cancer predisposition, including a 20% to 30% lifetime risk of lymphoid, gastric, breast, central nervous system, skin, and other cancers (PMID: 27413114). Deletion of ATM in mouse models and cell lines demonstrates that it is oncogenic as measured by decreased DNA repair efficiency and increased cellular motility (PMID: 30553448, 30348496). JAX-CKB: No results found

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Unknown
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.14 3 bp
- Donor Loss (DL) 0.0 -204 bp
+ Acceptor Gain (AG) 0.04 -3 bp
+ Donor Gain (DG) 0.01 84 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
PVS1

PVS1 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)