Genetic Information

Gene & Transcript Details

Gene
ATM
Transcript
NM_000051.4 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_000051.4:c.2222A>G
Protein Change
Y741C
Location
Exon 14 (Exon 14 of )
14
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.00142 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
Uncertain Significance (VUS)
2 publications
Publications List
Clinical Statement

"This variant has been reported in ClinVar as Uncertain significance (6 clinical laboratories) and as Likely benign (3 clinical laboratories)."

COSMIC Somatic Evidence

Open
COSMIC ID
COSM9568440
Recurrence
1 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: ATMY741CATMY741CSomaticNCBI 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 Y741C mutation has not specifically been reviewed by the OncoKB team, and therefore its biological significance is unknown. 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
Mixed/VUS
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.02 -97 bp
- Donor Loss (DL) 0.05 28 bp
+ Acceptor Gain (AG) 0.0 -15 bp
+ Donor Gain (DG) 0.29 -1 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:
PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)