Evidence Repository - Clinical Genome Resources

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_000051.3(ATM):c.1442T>G (p.Leu481Ter)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA382534080

453367 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f9cb171c-3f39-4add-9c85-9254d5f10266

Approved on: 2022-03-09

Published on: 2022-07-11

HGVS expressions

NM_000051.3:c.1442T>G

NM_000051.3(ATM):c.1442T>G (p.Leu481Ter)

NC_000011.10:g.108250907T>G

CM000673.2:g.108250907T>G

NC_000011.9:g.108121634T>G

CM000673.1:g.108121634T>G

NC_000011.8:g.107626844T>G

NG_009830.1:g.33076T>G

ENST00000278616.9:c.1442T>G

ENST00000682516.1:n.1576T>G

ENST00000682956.1:n.1576T>G

ENST00000683174.1:n.1592T>G

ENST00000683605.1:n.937T>G

ENST00000684037.1:c.*377T>G

ENST00000684061.1:n.1576T>G

ENST00000684179.1:n.1411T>G

ENST00000527805.6:c.1442T>G

ENST00000675595.1:c.1277T>G

ENST00000675843.1:c.1442T>G

ENST00000278616.8:c.1442T>G

ENST00000452508.6:c.1442T>G

ENST00000527805.5:c.1442T>G

NM_001351834.1:c.1442T>G

NM_001351834.2:c.1442T>G

NM_000051.4:c.1442T>G

NM_000051.4(ATM):c.1442T>G (p.Leu481Ter)

Pathogenic

PVS1 PM2_Supporting PM3_Strong PM5_Supporting

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 1.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The ATM c.1442T>G (p.Leu481Ter) variant is expected to produce an NMD-prone transcript due to a nonsense or frameshifting event (PVS1). In the absence of potential splicing rescue mechanisms in ATM, all PVS1-eligble truncating variants are expected to be pathogenic based on the existence of known pathogenic C-terminal truncations in the last exon (PM5_Supporting). This variant has been observed in a compound heterozygous state (confirmed) in one individual with Ataxia-Telangiectasia (PMID 21665257: PM3_Strong). This variant is absent in GnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the HBOP Variant Curation Expert Panel.

PVS1

Expected to produce an NMD-prone transcript due to a nonsense or frameshifting event (PVS1).

PM2_Supporting

This variant is absent in GnomAD v2.1.1 (PM2_Supporting).

PM3_Strong

This variant has been observed in a compound heterozygous state (confirmed) in one individual with Ataxia-Telangiectasia (PMID 21665257: PM3_Strong) (4 POINTS)

PM5_Supporting

In the absence of potential splicing rescue mechanisms in ATM, all PVS1-eligble truncating variants are expected to be pathogenic based on the existence of known pathogenic C-terminal truncations in the last exon (PM5_Supporting)

Curation History

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