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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000051.4(ATM):c.8161G>A (p.Asp2721Asn)

CA382562473

1054111 (ClinVar)

Gene: ATM (HGNC:472)
Condition: ATM-related cancer predisposition (MONDO:0700270)
Inheritance Mode: Autosomal dominant inheritance
UUID: 00607ef5-45d1-47af-8947-3ba6d6650812
Approved on: 2025-11-11
Published on: 2026-04-10

HGVS expressions

NM_000051.4(ATM):c.8161G>A (p.Asp2721Asn)
NM_000051.4:c.8161G>A
NC_000011.10:g.108335854G>A
CM000673.2:g.108335854G>A
NC_000011.9:g.108206581G>A
CM000673.1:g.108206581G>A
NC_000011.8:g.107711791G>A
NG_009830.1:g.118023G>A
NG_054724.1:g.138979C>T
ENST00000452508.7:c.8161G>A
ENST00000713593.1:c.*7632G>A
ENST00000278616.9:c.8161G>A
ENST00000525056.2:n.2580G>A
ENST00000638786.2:n.859G>A
ENST00000682286.1:n.2918G>A
ENST00000682302.1:n.2579G>A
ENST00000683174.1:n.9645G>A
ENST00000683524.1:n.3385G>A
ENST00000684152.1:n.3577G>A
ENST00000684180.1:n.635G>A
ENST00000684447.1:n.4654G>A
ENST00000527805.6:c.*3225G>A
ENST00000675595.1:c.*3296G>A
ENST00000675843.1:c.8161G>A
ENST00000278616.8:c.8161G>A
ENST00000452508.6:c.8161G>A
ENST00000524755.5:c.227-562C>T
ENST00000524792.5:n.4376G>A
ENST00000525056.1:n.358G>A
ENST00000525729.5:c.641-26783C>T
ENST00000527531.5:c.*1197-562C>T
ENST00000533979.5:n.373G>A
ENST00000615746.4:c.*1197-562C>T
NM_000051.3:c.8161G>A
NM_001330368.1:c.641-26783C>T
NM_001351110.1:c.695-562C>T
NM_001351834.1:c.8161G>A
NR_147053.2:n.2302-562C>T
NM_001330368.2:c.641-26783C>T
NM_001351110.2:c.695-562C>T
NM_001351834.2:c.8161G>A
NR_147053.3:n.2300-562C>T
More

Likely Pathogenic

Met criteria codes 4
PP1 PP3 PM3_Strong PM2_Supporting
Not Met criteria codes 22
PS2 PS4 PS3 PS1 PP4 PP2 PM6 PM4 PM1 PM5 BA1 BS2 PVS1 BS4 BS3 BS1 BP7 BP5 BP3 BP2 BP4 BP1

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 1.4.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hereditary Breast, Ovarian and Pancreatic Cancer VCEP
The c.8161G>A variant in ATM is a missense variant predicted to cause substitution of aspartic acid to asparagine at amino acid 2721 (p.Asp2721Asn). This variant has been detected in at least two unrelated individuals with Ataxia-Telangiectasia (PMID: 21665257, 25122203). The variant has been reported to segregate with Ataxia-Telangiectasia in two affected family members from one family (PMID: 25122203). This variant is absent from gnomAD v4.1.0. The computational predictor REVEL gives a score of 0.957, which is above the threshold of 0.7333, 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, PM2_Supporting)
Met criteria codes
PP1
Two siblings with confirmed diagnosis of A-T and nonsense variant in trans. Parents are confirmed to be carriers (internal communication, PMID: 25122203). Meets PP1_met as 1 segregation event is present.
PP3
The REVEL score is 0.957 which is above the threshold for pathogenicity. SpliceAI scores show a very low risk of an impact on splicing.
PM3_Strong
One patient with clinical diagnosis found with variant in PMID: 21665257 - second variant not specified. Therefore 1 point assigned. Two patients with A-T diagnosis (internal communication confirmed they are siblings) found with nonsense variant (c.7456C.T/p.R2486X), phase confirmed in PMID: 25122203. Assigned 4 points for one patient. Therefore 5 points in total = PM3_Strong
PM2_Supporting
This variant is absent from gnomADv4.
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
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
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
This variant is absent from gnomADv4.
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
This variant is absent from gnomADv4.
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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