Variant: NM_000051.4(ATM):c.5005+1G>T

CA16041413

371636 (ClinVar)

Gene: ATM

Condition: ATM-related cancer predisposition

Inheritance Mode: Autosomal dominant inheritance

UUID: f2c45aa0-d48d-42cc-897e-3103827a3330

Approved on: 2024-11-26

Published on: 2025-01-13

HGVS expressions

NM_000051.4:c.5005+1G>T
NM_000051.4(ATM):c.5005+1G>T
NC_000011.10:g.108297383G>T
CM000673.2:g.108297383G>T
NC_000011.9:g.108168110G>T
CM000673.1:g.108168110G>T
NC_000011.8:g.107673320G>T
NG_009830.1:g.79552G>T
ENST00000452508.7:c.5005+1G>T
ENST00000713593.1:c.*4476+1G>T
ENST00000278616.9:c.5005+1G>T
ENST00000683174.1:n.6489+1G>T
ENST00000683524.1:n.229+1G>T
ENST00000684152.1:n.719+1G>T
ENST00000527805.6:c.*69+1G>T
ENST00000675595.1:c.*69+1G>T
ENST00000675843.1:c.5005+1G>T
ENST00000278616.8:c.5005+1G>T
ENST00000452508.6:c.5005+1G>T
ENST00000524792.5:n.1220+1G>T
ENST00000533690.5:n.409+1G>T
NM_000051.3:c.5005+1G>T
NM_001351834.1:c.5005+1G>T
NM_001351834.2:c.5005+1G>T

Likely Pathogenic

• Met criteria codes: PVS1_Strong PM2_Supporting PM3

Expert Panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

Criteria Specification Information

Criteria Specification: ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ATM Version 1.3.0

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The c.5005+1G>T variant in ATM occurs within the canonical splice donor site (+1,2) of intron 33. It is predicted to cause skipping of a biologically-relevant-exon, resulting in an in-frame deletion that is predicted to escape nonsense mediated decay. This variant has been detected in at least 1 individual with Ataxia-Telangiectasia (PMID: 26896183). This variant is absent from gnomAD v2.1.1. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal dominant ATM-related cancer predisposition and autosomal recessive Ataxia-Telangiectasia based on the ACMG/AMP criteria applied, as specified by the HBOP Variant Curation Expert Panel. (PVS1_Strong, PM3, PM2_Supporting)

Met criteria codes

• PVS1_Strong: The c.5005+1G>T variant in ATM occurs within the canonical splice donor site (+/- 1,2) of intron 33. It is predicted to cause skipping of biologically-relevant-exon 33, resulting in an in-frame deletion that is predicted to escape nonsense mediated decay (PVS1_Strong).
• PM2_Supporting: This variant is absent from gnomAD v2.1.1
• PM3: This variant has been detected in 1 individual with ataxia-telangiectasia (PMID:26896183, PM3_Moderate).