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.8520G>C (p.Leu2840Phe)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA348719

221124 (ClinVar)

Gene: ATM

Condition: ATM-related cancer predisposition

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b795eb4f-8bfd-4c3f-be06-ed5189f4647e

Approved on: 2024-11-26

Published on: 2025-01-13

HGVS expressions

NM_000051.4:c.8520G>C

NM_000051.4(ATM):c.8520G>C (p.Leu2840Phe)

NC_000011.10:g.108345844G>C

CM000673.2:g.108345844G>C

NC_000011.9:g.108216571G>C

CM000673.1:g.108216571G>C

NC_000011.8:g.107721781G>C

NG_009830.1:g.128013G>C

NG_054724.1:g.128989C>G

ENST00000452508.7:c.8520G>C

ENST00000713593.1:c.*7991G>C

ENST00000278616.9:c.8520G>C

ENST00000638786.2:n.1218G>C

ENST00000682286.1:n.3277G>C

ENST00000682302.1:n.2938G>C

ENST00000683174.1:n.10004G>C

ENST00000683524.1:n.3744G>C

ENST00000684152.1:n.3936G>C

ENST00000684180.1:n.994G>C

ENST00000684447.1:n.5013G>C

ENST00000527805.6:c.*3584G>C

ENST00000675595.1:c.*3655G>C

ENST00000675843.1:c.8520G>C

ENST00000278616.8:c.8520G>C

ENST00000452508.6:c.8520G>C

ENST00000524755.5:c.227-10552C>G

ENST00000524792.5:n.4735G>C

ENST00000525729.5:c.641-36773C>G

ENST00000526725.1:n.272-5480C>G

ENST00000527531.5:c.*1196+9071C>G

ENST00000615746.4:c.*1196+9071C>G

NM_000051.3:c.8520G>C

NM_001330368.1:c.641-36773C>G

NM_001351110.1:c.695-10552C>G

NM_001351834.1:c.8520G>C

NR_147053.2:n.2301+9071C>G

NM_001330368.2:c.641-36773C>G

NM_001351110.2:c.695-10552C>G

NM_001351834.2:c.8520G>C

NR_147053.3:n.2299+9071C>G

Uncertain Significance

PM3 PM2_Supporting

PP3 BP4

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 1.3.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The c.8520G>C variant in ATM is a missense variant predicted to cause substitution of leucine by phenylalanine at amino acid 2840 (p.Leu2840Phe). This variant has been detected in at least one individual with Ataxia-Telangiectasia (PMID: 26896183, 22649200). This variant is absent from gnomAD v2.1.1. The computational predictor REVEL gives a score of 0.464, which is neither above nor below the thresholds predicting a damaging or benign impact on ATM function. In summary, this variant meets criteria to be classified as a variant of uncertain significance for autosomal dominant ATM-related cancer predisposition and autosomal recessive Ataxia-Telangiectasia based on the ACMG/AMP criteria applied, as specified by the HBOP VCEP. (PM3, PM2_Supporting)

PM3

2 pts; PM3_moderate; This variant has been detected in at least one individual with Ataxia-Telangiectasia (PMID: 26896183; PMID: 22649200)

PM2_Supporting

This variant is absent from gnomAD v2.1.1.

PP3

Revel Score: 0.464; The computational predictor, Revel, gives a score of 0.464, which is neither above nor below the thresholds predicting a damaging or benign impact on ATM function.

BP4

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

Curation History

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