Evidence Repository
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.3078-1G>A

CA6265193

231277 (ClinVar)

Gene: ATM
Condition: hereditary breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 815cc1ba-f95b-44a2-ada7-6c5d57d608e6
Approved on: 2024-01-25
Published on: 2024-02-14

HGVS expressions

NM_000051.4:c.3078-1G>A
NM_000051.4(ATM):c.3078-1G>A
NC_000011.10:g.108272531G>A
CM000673.2:g.108272531G>A
NC_000011.9:g.108143258G>A
CM000673.1:g.108143258G>A
NC_000011.8:g.107648468G>A
NG_009830.1:g.54700G>A
ENST00000452508.7:c.3078-1G>A
ENST00000713593.1:c.*2549-1G>A
ENST00000278616.9:c.3078-1G>A
ENST00000683174.1:n.3228-1G>A
ENST00000527805.6:c.3078-1G>A
ENST00000675595.1:c.2913-1G>A
ENST00000675843.1:c.3078-1G>A
ENST00000278616.8:c.3078-1G>A
ENST00000452508.6:c.3078-1G>A
ENST00000527805.5:c.3078-1G>A
NM_000051.3:c.3078-1G>A
NM_001351834.1:c.3078-1G>A
NM_001351834.2:c.3078-1G>A
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Pathogenic

Met criteria codes 2
PM3_Strong PVS1
Not Met criteria codes 2
PM5 PM2

Evidence Links 0

Expert Panel

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 c.3078-1G>A variant in ATM occurs within the canonical splice donor/acceptor site (+/- 1,2) of intron 20. It is predicted to cause skipping of a biologically-relevant-exon, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism. The highest population minor allele frequency in gnomAD v2.1.1 is (0. 0.0018%) (2/113536 alleles) in the European (non-Finnish) population. (PM2_Supporting, BS1, and BA1 are not met). This variant has been detected in at least 1 individual with Ataxia-Telangiectasia (PMID: 10234507). 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_Strong).
Met criteria codes
PM3_Strong
This variant has been detected in at least 1 individual with Ataxia-Telangiectasia in the compound heterozygous state for the variant and a pathogenic or likely pathogenic variant, confirmed in trans. (PMID: 10234507).
PVS1
The c.3078-1G>A variant in ATM occurs within the canonical splice donor/acceptor site (+/- 1,2) of intron 20. It is predicted to cause skipping of a biologically-relevant-exon, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism.
Not Met criteria codes
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest population minor allele frequency in gnomAD v2.1.1 is [0. 0.0018%] (2/113536 alleles) in the European (non-Finnish) population. (PM2_Supporting, BS1, and BA1 are not met)
Curation History
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