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
  • Despite there being a valid 'cspec' property in the messages there's a discrepancy in message contents and CSPEC data: * Message Gene: ATM CSPEC Genes: [ 'ATM' ] * Message MONDOs: MONDO:0700270 CSPEC MONDO: [ 'MONDO:0016419', 'MONDO:0008840', 'MONDO:0018266' ]
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000051.4(ATM):c.8395_8404del (p.Phe2799fs)

CA194225

186242 (ClinVar)

Gene: ATM
Condition: ATM-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e90af0fd-26d7-4c79-a519-c1b3a2772f61
Approved on: 2024-11-26
Published on: 2025-01-13

HGVS expressions

NM_000051.4:c.8395_8404delTTTCAGTGCC
NM_000051.4:c.8395_8404del
NM_000051.4(ATM):c.8395_8404del (p.Phe2799fs)
NC_000011.10:g.108343348_108343357del
CM000673.2:g.108343348_108343357del
NC_000011.9:g.108214075_108214084del
CM000673.1:g.108214075_108214084del
NC_000011.8:g.107719285_107719294del
NG_009830.1:g.125517_125526del
NG_054724.1:g.131486_131495del
ENST00000452508.7:c.8395_8404del
ENST00000713593.1:c.*7866_*7875del
ENST00000278616.9:c.8395_8404del
ENST00000638786.2:n.1093_1102del
ENST00000682286.1:n.3152_3161del
ENST00000682302.1:n.2813_2822del
ENST00000683174.1:n.9879_9888del
ENST00000683524.1:n.3619_3628del
ENST00000684152.1:n.3811_3820del
ENST00000684180.1:n.869_878del
ENST00000684447.1:n.4888_4897del
ENST00000527805.6:c.*3459_*3468del
ENST00000675595.1:c.*3530_*3539del
ENST00000675843.1:c.8395_8404del
ENST00000278616.8:c.8395_8404del
ENST00000452508.6:c.8395_8404del
ENST00000524755.5:c.227-8055_227-8046del
ENST00000524792.5:n.4610_4619del
ENST00000525729.5:c.641-34276_641-34267del
ENST00000526725.1:n.272-2983_272-2974del
ENST00000527531.5:c.*1197-8055_*1197-8046del
ENST00000615746.4:c.*1197-8055_*1197-8046del
NM_000051.3:c.8395_8404del
NM_001330368.1:c.641-34276_641-34267del
NM_001351110.1:c.695-8055_695-8046del
NM_001351834.1:c.8395_8404del
NR_147053.2:n.2302-8055_2302-8046del
NM_001330368.2:c.641-34276_641-34267del
NM_001351110.2:c.695-8055_695-8046del
NM_001351834.2:c.8395_8404del
NR_147053.3:n.2300-8055_2300-8046del
More

Pathogenic

Met criteria codes 3
PM5_Supporting PVS1 PM3_Very Strong
Not Met criteria codes 3
PM2 BS1 BA1

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 1.3.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hereditary Breast, Ovarian and Pancreatic Cancer VCEP
The c.8395_8404del (p.Phe2799Lysfs*4) variant in ATM is a frameshift variant in a biologically-relevant-exon predicted to cause a premature stop codon leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism. This alteration results in a termination codon upstream of the most C-terminus pathogenic alteration (ATM p.Arg3047*), as classified by the HBOP VCEP, and is expected to be more deleterious. This variant has been detected in at least 7 individuals with Ataxia-Telangiectasia (PMID: 9792409, 9887333, 10817650, 12815592, 19147735, 21833744, 26896183). The highest population minor allele frequency in gnomAD v2.1.1 is 0.000026 in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). In summary, this variant meets the criteria to be classified as 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. (PVS1, PM5_supporting, PM3_Very Strong)
Met criteria codes
PM5_Supporting
This alteration results in a termination codon upstream of the most C-terminus pathogenic alteration (ATM p.Arg3047*), as classified by the HBOP VCEP, and is expected to be more deleterious.
PVS1
The c.8395_8404del p.Phe2799LysfsTer4 variant in ATM is a frameshift variant in a biologically-relevant-exon predicted to cause a premature stop codon leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism.
PM3_Very Strong
This variant has been detected in at least 7 individuals with Ataxia-Telangiectasia (15 points, PMIDs 19147735, 21833744, 12815592, 10817650, 9887333, 9792409, 26896183: PM3_VeryStrong)
Not Met criteria codes
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
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
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