Evidence Repository - GenboreeKB

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000051.4:c.1782del

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA2497029997

Gene: ATM

Condition: ATM-related cancer predisposition

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3a9f00cf-93c6-4a4d-ae4e-e6cbcc8a794c

Approved on: 2024-11-26

Published on: 2025-01-13

HGVS expressions

NM_000051.4:c.1782del

NC_000011.10:g.108252011del

CM000673.2:g.108252011del

NC_000011.9:g.108122738del

CM000673.1:g.108122738del

NC_000011.8:g.107627948del

NG_009830.1:g.34180del

ENST00000452508.7:c.1782del

ENST00000713593.1:c.*1253del

ENST00000278616.9:c.1782del

ENST00000682516.1:n.1916del

ENST00000683174.1:n.1932del

ENST00000683605.1:n.1277del

ENST00000684037.1:c.*717del

ENST00000684061.1:n.1916del

ENST00000527805.6:c.1782del

ENST00000675595.1:c.1617del

ENST00000675843.1:c.1782del

ENST00000278616.8:c.1782del

ENST00000452508.6:c.1782del

ENST00000527805.5:c.1782del

NM_000051.3:c.1782del

NM_001351834.1:c.1782del

NM_001351834.2:c.1782del

Pathogenic

PM2 PM3 PM5_Supporting PVS1

Evidence Links 0

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The c.1782del (p.Val595Cysfs*19) variant in ATM gene is a frameshift variant observed to cause a premature stop codon in biologically-relevant-exon leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism. This alteration results in a termination codon upstream of the most C-terminal pathogenic alteration (ATM p.Arg3047*), as classified by the HBOP VCEP, and is expected to be more deleterious. This variant has been detected in at least one individual with Ataxia-Telangiectasia (PMID: 26896183). This variant is absent from gnomAD v.2.1.1. In summary, this variant meets the criteria to be classified as 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 VCEP. (PVS1, PM5_Supporting, PM3, PM2_Supporting)

PM2

Absent in gnomAD population database

PM3

The c.1782del (p.Val595CysfsTer19) variant has been detected in one individual with Ataxia-Telangiectasia (2 points: PMID: 26896183) Second variant (c.5228C>T) (Likely pathogenic)

PM5_Supporting

The c.1782del (p.Val595CysfsTer19) variant alteration results in a termination codon upstream of the most C-terminus pathogenic alteration (ATM p.Arg3047*), as classified by the HBOP VCEP, and is expected to be deleterious(PM5_Supporting).

PVS1

The c.1782del(p.Val595CysfsTer19) variant in ATM gene is a frameshift variant observed to cause premature truncation of the protein in exon 10/63 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism.

Curation History

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