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.3925G>A (p.Ala1309Thr)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA242620

127377 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 65d2266d-93af-405f-b678-b9b808d3bbe1

Approved on: 2022-03-09

Published on: 2022-07-11

HGVS expressions

NM_000051.4:c.3925G>A

NM_000051.4(ATM):c.3925G>A (p.Ala1309Thr)

NC_000011.10:g.108284405G>A

CM000673.2:g.108284405G>A

NC_000011.9:g.108155132G>A

CM000673.1:g.108155132G>A

NC_000011.8:g.107660342G>A

NG_009830.1:g.66574G>A

ENST00000278616.9:c.3925G>A

ENST00000682289.1:n.272G>A

ENST00000683174.1:n.4075G>A

ENST00000527805.6:c.3925G>A

ENST00000675595.1:c.3760G>A

ENST00000675843.1:c.3925G>A

ENST00000278616.8:c.3925G>A

ENST00000452508.6:c.3925G>A

ENST00000527805.5:c.3925G>A

NM_000051.3:c.3925G>A

NM_001351834.1:c.3925G>A

NM_001351834.2:c.3925G>A

Benign

BS1 BP4 BP2_Strong

PM2 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.3925G>A (p.Ala1309Thr) variant has a GnomAD (v2.1.1) filtering allele frequency of 0.1050% (NFE) which is above the ATM BS1 threshold of .05% (BS1). This variant has been observed in a homozygous and compound heterozygous state in multiple individuals without ataxia-telangiectasia (Internal laboratory contributions; BP2_strong). Multiple in silico protein predictors predict that this alteration is not deleterious (BP4). In summary, this variant meets criteria to be classified as benign based on the ACMG/AMP criteria applied, as specified by the HBOP Variant Curation Expert Panel.

BS1

This variant has a GnomAD (v2.1.1) filtering allele frequency of 0.1050% (NFE) which is above the ATM BS1 threshold of .05% (BS1).

BP4

In silico protein predictors (Revel, 0.076), (SIFT, 0.084, 0.118, 0.118), (PolyPhen2-HDIV, 0.009, 0.009), PolyPhen2-HVAR (0.015, 0.015) predict that this alteration is not deleterious (BP4).

BP2_Strong

This variant has been observed in a homozygous and/or compound heterozygous state (presumed and/or confirmed) in multiple individuals without Ataxia-Telangiectasia (Internal laboratory contributions BP2_strong) (-12pts)

PM2

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

Curation History

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.