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_000051.4(ATM):c.8786+1G>A

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA274150

127463 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: c0af412b-1446-4897-b7a3-43d57fec76fc

Approved on: 2024-01-25

Published on: 2024-02-14

HGVS expressions

NM_000051.4:c.8786+1G>A

NM_000051.4(ATM):c.8786+1G>A

NC_000011.10:g.108353881G>A

CM000673.2:g.108353881G>A

NC_000011.9:g.108224608G>A

CM000673.1:g.108224608G>A

NC_000011.8:g.107729818G>A

NG_009830.1:g.136050G>A

NG_054724.1:g.120952C>T

ENST00000452508.7:c.8786+1G>A

ENST00000713593.1:c.*8257+1G>A

ENST00000278616.9:c.8786+1G>A

ENST00000638786.2:n.1484+1G>A

ENST00000682286.1:n.3543+1G>A

ENST00000682302.1:n.3204+1G>A

ENST00000683174.1:n.10270+1G>A

ENST00000683524.1:n.4010+1G>A

ENST00000684152.1:n.4202+1G>A

ENST00000684180.1:n.1260+1G>A

ENST00000684447.1:n.5279+1G>A

ENST00000527805.6:c.*3850+1G>A

ENST00000675595.1:c.*3921+1G>A

ENST00000675843.1:c.8786+1G>A

ENST00000278616.8:c.8786+1G>A

ENST00000452508.6:c.8786+1G>A

ENST00000524755.5:c.227-18589C>T

ENST00000524792.5:n.5001+1G>A

ENST00000525178.5:n.274+1G>A

ENST00000525729.5:c.640+32039C>T

ENST00000526725.1:n.272-13517C>T

ENST00000527181.1:n.125+1G>A

ENST00000527531.5:c.*1196+1034C>T

ENST00000615746.4:c.*1196+1034C>T

NM_000051.3:c.8786+1G>A

NM_001330368.1:c.640+32039C>T

NM_001351110.1:c.695-18589C>T

NM_001351834.1:c.8786+1G>A

NR_147053.2:n.2301+1034C>T

NM_001330368.2:c.640+32039C>T

NM_001351110.2:c.695-18589C>T

NM_001351834.2:c.8786+1G>A

NR_147053.3:n.2299+1034C>T

Pathogenic

PM3_Strong PVS1

PM2

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 1.2.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The ATM c.8786+1G>A variant occurs within the canonical splice donor site (+/- 1,2) of intron 60. It is predicted to cause skipping of a biologically-relevant-exon, resulting in a premature stop codon and nonsense mediated decay. The highest minor allele frequency in gnomAD v2.1.1 is 0.00003517 (4/113738) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). This variant has been detected in at least 6 individuals with Ataxia-Telangiectasia (PMID: 26896183, 10817650, 9463314). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant hereditary breast cancer and autosomal recessive Ataxia-Telangiectasia based on the ACMG/AMP criteria applied, as specified by the HBOP VCEP. (PVS1, PM3_very strong)

PM3_Strong

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

PVS1

The c.8786+1G>A variant in ATM occurs within the canonical splice donor site (+/- 1,2) of intron 60. It is predicted to cause skipping of biologically-relevant-exon 61, resulting in a premature stop codon and NMD (PVS1).

PM2

This variant has a minor allele frequency in gnomAD v2.1.1 of 0.00003517 (4/113738) in the European (non-Finnish) population (PM2_Supporting not met).

Curation History

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