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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000051.4(ATM):c.6997dup

CA345709

140818 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: bf976c78-5c26-4e5b-bfcf-375b219c72be

Approved on: 2022-03-16

Published on: 2022-07-12

HGVS expressions

NM_000051.4:c.6997dup

NM_000051.4(ATM):c.6997dup

NC_000011.10:g.108327666dup

CM000673.2:g.108327666dup

NC_000011.9:g.108198393dup

CM000673.1:g.108198393dup

NC_000011.8:g.107703603dup

NG_009830.1:g.109835dup

NG_054724.1:g.147167dup

ENST00000278616.9:c.6997dup

ENST00000525056.2:n.1416dup

ENST00000682286.1:n.1754dup

ENST00000682302.1:n.1415dup

ENST00000683174.1:n.8481dup

ENST00000683524.1:n.2221dup

ENST00000684152.1:n.2711dup

ENST00000684447.1:n.1460dup

ENST00000527805.6:c.*2061dup

ENST00000675595.1:c.*2132dup

ENST00000675843.1:c.6997dup

ENST00000278616.8:c.6997dup

ENST00000452508.6:c.6997dup

ENST00000524792.5:n.3212dup

ENST00000525537.2:n.273dup

ENST00000525729.5:c.641-18595dup

ENST00000527389.2:n.22dup

ENST00000533690.5:n.2401dup

NM_000051.3:c.6997dup

NM_001330368.1:c.641-18595dup

NM_001351110.1:c.*38+7554dup

NM_001351834.1:c.6997dup

NM_001330368.2:c.641-18595dup

NM_001351110.2:c.*38+7554dup

NM_001351834.2:c.6997dup

Pathogenic

PM2_Supporting PVS1 PM5_Supporting PM3_Strong

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.6997dupA (p.Thr2333Nfs*40) 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 (presumed) or with a second variant unidentified in four individuals with Ataxia-Telangiectasia (PMID 21459046, 10817650, 9463314, Clinical Laboratory Data: PM3_Strong). Variant is absent in the GnomAD v2.1.1 cohort (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

PM2_Supporting

Variant is absent in the GnomAD v2.1.1 cohort (PM2_Supporting).

PVS1

Nonsense/Frameshift; NMD Prone

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)

PM3_Strong

This variant has been observed in a homozygous and/or compound heterozygous state (presumed and/or confirmed) in one/multiple individuals with Ataxia-Telangiectasia (PM3_Strong) (5 POINTS)

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