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.8486C>T (p.Pro2829Leu)

CA16619259

418777 (ClinVar)

Gene: ATM (HGNC:472)

Condition: ATM-related cancer predisposition (MONDO:0700270)

Inheritance Mode: Autosomal dominant inheritance

UUID: 13918561-f552-46bc-a22c-f090b5a93152

Approved on: 2026-08-04

Published on: 2026-08-05

HGVS expressions

NM_000051.4:c.8486C>T

NM_000051.4(ATM):c.8486C>T (p.Pro2829Leu)

NC_000011.10:g.108345810C>T

CM000673.2:g.108345810C>T

NC_000011.9:g.108216537C>T

CM000673.1:g.108216537C>T

NC_000011.8:g.107721747C>T

NG_009830.1:g.127979C>T

NG_054724.1:g.129023G>A

ENST00000452508.7:c.8486C>T

ENST00000713593.1:c.*7957C>T

ENST00000278616.9:c.8486C>T

ENST00000638786.2:n.1184C>T

ENST00000682286.1:n.3243C>T

ENST00000682302.1:n.2904C>T

ENST00000683174.1:n.9970C>T

ENST00000683524.1:n.3710C>T

ENST00000684152.1:n.3902C>T

ENST00000684180.1:n.960C>T

ENST00000684447.1:n.4979C>T

ENST00000527805.6:c.*3550C>T

ENST00000675595.1:c.*3621C>T

ENST00000675843.1:c.8486C>T

ENST00000278616.8:c.8486C>T

ENST00000452508.6:c.8486C>T

ENST00000524755.5:c.227-10518G>A

ENST00000524792.5:n.4701C>T

ENST00000525729.5:c.641-36739G>A

ENST00000526725.1:n.272-5446G>A

ENST00000527531.5:c.*1196+9105G>A

ENST00000615746.4:c.*1196+9105G>A

NM_000051.3:c.8486C>T

NM_001330368.1:c.641-36739G>A

NM_001351110.1:c.695-10518G>A

NM_001351834.1:c.8486C>T

NR_147053.2:n.2301+9105G>A

NM_001330368.2:c.641-36739G>A

NM_001351110.2:c.695-10518G>A

NM_001351834.2:c.8486C>T

NR_147053.3:n.2299+9105G>A

Likely Pathogenic

PM3_Strong PP1 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 1.5

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The c.8486C>T variant in ATM is a missense variant predicted to cause substitution of proline by leucine at amino acid 2829 (p.Pro2829Leu). This variant has been detected in individual(s) with Ataxia-Telangiectasia (personal communication; PMID: 9711876; PMID: 37438524). This variant has been reported to segregate with Ataxia-Telangiectasia in two affected individuals from one family (personal communication). The highest population minor allele frequency in gnomAD v4.1.0 is 0.00001667 in the Admixed American population (PM2_Supporting, BS1, and BA1 are not met). The computational predictor REVEL gives a score of 0.952, which is above the threshold of 0.733, evidence that correlates with impact to ATM function. In summary, this variant meets the criteria to be classified as likely pathogenic 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_Strong, PP1, PP3)

PM3_Strong

This variant has been detected in 3 individuals with Ataxia-Telangiectasia. Of those individuals, two were confirmed in trans by family testing (personal communication). One individual was homozygous for the variant (PMID: 9711876; PMID: 37438524)(PM3_Strong).

PP1

This variant has been reported to segregate with Ataxia-Telangiectasia in two affected individuals from one family (personal communication)

PP3

The computational predictor REVEL gives a score of 0.952, which is above the threshold of 0.733, evidence that correlates with impact to ATM function (PP3). SpliceAI does not predict any aberrant splicing associated with this variant.

PM2

The highest population minor allele frequency in gnomAD v4 is 0.000016 (1/60002 alleles) in Admixed American population which is higher than the ClinGen HBOP threshold 0.001% for PM2_Supporting

Curation History

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