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_000051.3(ATM):c.1607+1G>T

CA348209

220555 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e356a4a5-315c-40ed-834e-1c861ad5a22a

HGVS expressions

NM_000051.3:c.1607+1G>T

NM_000051.3(ATM):c.1607+1G>T

NC_000011.10:g.108251073G>T

CM000673.2:g.108251073G>T

NC_000011.9:g.108121800G>T

CM000673.1:g.108121800G>T

NC_000011.8:g.107627010G>T

NG_009830.1:g.33242G>T

ENST00000278616.9:c.1607+1G>T

ENST00000682516.1:n.1741+1G>T

ENST00000682956.1:n.1742G>T

ENST00000683174.1:n.1757+1G>T

ENST00000683605.1:n.1102+1G>T

ENST00000684037.1:c.*542+1G>T

ENST00000684061.1:n.1741+1G>T

ENST00000684179.1:n.1577G>T

ENST00000527805.6:c.1607+1G>T

ENST00000675595.1:c.1442+1G>T

ENST00000675843.1:c.1607+1G>T

ENST00000278616.8:c.1607+1G>T

ENST00000452508.6:c.1607+1G>T

ENST00000527805.5:c.1607+1G>T

NM_001351834.1:c.1607+1G>T

NM_001351834.2:c.1607+1G>T

NM_000051.4:c.1607+1G>T

NM_000051.4(ATM):c.1607+1G>T

Pathogenic

PM2_Supporting PM3_Very Strong PVS1_Strong

BS1 BA1

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.1607+1G>T canonical splice variant is predicted to result in a truncated protein that disrupts a critical functional domain (PVS1_Strong). This variant has been observed in a homozygous and compound heterozygous state in multiple individuals with Ataxia-Telangiectasia (PMIDs: 10330348, 1712434, 9450906, 19691550, PM3_VeryStrong). This variant has a GnomAD (v2.1.1) allele frequency of 0.0009% (NFE) which is below the ATM PM2 threshold of 0.001% (PM2_Supporting). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the HBOP Variant Curation Expert Panel.

PM2_Supporting

This variant has a GnomAD (v2.1.1) allele frequency of 0.0009% (NFE) which is below the ATM PM2 threshold of 0.001% (PM2_Supporting).

PM3_Very 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 (PMIDs: 10330348, 1712434, 9450906) (8 points)

PVS1_Strong

The c.1607+1G>T canonical splice variant is predicted to result in a truncated protein that disrupts a critical functional domain (PVS1_Strong).

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2022-03-16

Published on: 2022-07-12

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.