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.6995T>C (p.Leu2332Pro)

CA157165

133631 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d85e41f7-7a25-4f0c-b2eb-530a536f48f4

Approved on: 2022-03-09

Published on: 2022-07-11

HGVS expressions

NM_000051.3:c.6995T>C

NM_000051.3(ATM):c.6995T>C (p.Leu2332Pro)

NC_000011.10:g.108327664T>C

CM000673.2:g.108327664T>C

NC_000011.9:g.108198391T>C

CM000673.1:g.108198391T>C

NC_000011.8:g.107703601T>C

NG_009830.1:g.109833T>C

NG_054724.1:g.147169A>G

ENST00000278616.9:c.6995T>C

ENST00000525056.2:n.1414T>C

ENST00000682286.1:n.1752T>C

ENST00000682302.1:n.1413T>C

ENST00000683174.1:n.8479T>C

ENST00000683524.1:n.2219T>C

ENST00000684152.1:n.2709T>C

ENST00000684447.1:n.1458T>C

ENST00000527805.6:c.*2059T>C

ENST00000675595.1:c.*2130T>C

ENST00000675843.1:c.6995T>C

ENST00000278616.8:c.6995T>C

ENST00000452508.6:c.6995T>C

ENST00000524792.5:n.3210T>C

ENST00000525537.2:n.271T>C

ENST00000525729.5:c.641-18593A>G

ENST00000527389.2:n.20T>C

ENST00000533690.5:n.2399T>C

NM_001330368.1:c.641-18593A>G

NM_001351110.1:c.*38+7556A>G

NM_001351834.1:c.6995T>C

NM_001330368.2:c.641-18593A>G

NM_001351110.2:c.*38+7556A>G

NM_001351834.2:c.6995T>C

NM_000051.4:c.6995T>C

NM_000051.4(ATM):c.6995T>C (p.Leu2332Pro)

Benign

BP4 BA1 BP2_Strong

BS1 PS1 PP3 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 1.1

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.6995T>C (p.Leu2332Pro) variant has a gnomAD v2.1.1 filtering allele frequency of 2.062% (African/African-American; exomes) which exceeds the ATM BA1 threshold of 0.50% (BA1). This variant has been observed in a homozygous and compound heterozygous state (presumed) in multiple individuals without biallelic disease (BP2_Strong; GTR Lab IDs: 61756, 500031). In silico protein predictors (ALIGN GVGD: Class C25; REVEL: 0.193; SIFT: tolerated; PolyPhen2: benign) predict that this alteration is not deleterious and in silico splicing predictors (SpliceAI: AL 0.01/DL 0.00/AG 0.00/DG 0.00; MaxEntScan: 0.00% (wild type = 9.04, variant = 9.04)) find that this variant is unlikely to affect splicing (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.

BP4

In silico protein predictors (ALIGN GVGD: Class C25; REVEL: 0.193; SIFT: tolerated; PolyPhen2: benign) predict that this alteration is not deleterious and in silico splicing predictors (SpliceAI: AL 0.01/DL 0.00/AG 0.00/DG 0.00; MaxEntScan: 0.00% (wild type = 9.04, variant = 9.04)) find that this variant is unlikely to affect splicing (BP4).

BA1

GnomAD v2.1.1 FAF 2.062% (African/African-American; exomes) exceeds ATM BA1 threshold of 0.50%.

BP2_Strong

This variant has been observed in a homozygous and compound heterozygous state (presumed) in multiple individuals without biallelic disease (BP2_Strong; GTR Lab IDs: 61756, 500031).

BS1

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

PS1

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

PP3

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

PM2

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

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