About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.9139C>T, p.(Arg3047Ter)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen ATM VCEP v1.5.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PVS1Very strong
PVS1 · very strong
NM_000051.4:c.9139C>T is a nonsense variant producing p.Arg3047Ter in ATM, a gene where loss of function is a well-established disease mechanism. The VCEP explicitly identifies p.Arg3047 as the most C-terminal residue considered pathogenic (PMIDs: 8755918, 19691550, 18560558, 10980530, 26628246). This null variant truncates the ATM protein within the FATC domain (exon 63, the terminal coding exon). Per the ATM PVS1 Decision Tree, PVS1 is applied at very strong strength.
PP5Supporting
PP5 · supporting
Expert panel ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen classified as Pathogenic.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework was evaluated deterministically with applied criteria: PVS1 very strong, PP5 supporting; no rule matched the adjudicated criteria.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
26 / 1,613,988 alleles
gnomAD v4.1: 26 / 1,613,988 alleles. Recorded AF 1.61092e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.76778e-05; MAF= 0.00177%, 5/282840 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 9.80072e-05; MAF= 0.00980%, 3/30610 alleles, homozygotes = 0); grpmax FAF= 2.596e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.150 maximum delta
Recorded SpliceAI maximum delta score: 0.150. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
18 reported laboratory submissions
18 Pathogenic.
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
18 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV53724126, n = 18 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen ATM VCEP v1.5.0, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 10 not met · 0 not assessed · 17 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000051.4:c.9139C>T (p.Arg3047Ter) is a nonsense variant in exon 63 of ATM, creating a premature termination codon at the most C-terminal residue considered pathogenic by the HBOP VCEP (p.Arg3047). PVS1 is applied at very strong strength under the ATM PVS1 Decision Tree as a null variant in a gene where loss of function is a known disease mechanism.
This variant has been reported in ClinVar as Pathogenic by the ClinGen HBOP VCEP expert panel and by 18 clinical laboratories (ClinVar Variation ID: 3029).
The variant is present in gnomAD v4.1 at an extremely low frequency (AF=1.61×10⁻⁵, 26/1,613,988 alleles; no homozygotes), consistent with a rare disease-causing variant. It is also present in gnomAD v2.1 at similar frequency (AF=1.77×10⁻⁵, 5/282,840 alleles).
Functional characterization by Guo et al. (2010, PMID 21150274) demonstrates that the R3047X mutant protein is expressed but specifically deficient in oxidation-dependent ATM activation while retaining MRN/DNA-dependent activation. Cells from an A-T patient with this variant showed moderate radiosensitivity, consistent with preserved DNA damage response but lost oxidative stress signaling.
Chessa et al. (2009, PMID 19691550) identified c.9139C>T in two Italian A-T families from Central Italy, confirming observation of this variant in individuals with classical ataxia-telangiectasia.
No VCEP-approved functional assay data, case-control studies, or detailed co-segregation data were available from the reviewed sources. Additional supporting evidence may exist in curated databases not accessible in this assessment. The ClinGen expert panel classification of Pathogenic likely incorporates proband data and/or additional supporting criteria not available here.
No criteria match.
Met · 2
PVS1 Very strongNM_000051.4:c.9139C>T is a nonsense variant producing p.Arg3047Ter in ATM, a gene where loss of function is a well-established disease mechanism. The VCEP explicitly identifies p.Arg3047 as the most C-terminal residue considered pathogenic (PMIDs: 8755918, 19691550, 18560558, 10980530, 26628246). This null variant truncates the ATM protein within the FATC domain (exon 63, the terminal coding exon). Per the ATM PVS1 Decision Tree, PVS1 is applied at very strong strength. Details ▾Hide ▴
Evidence considered
- Nonsense variant (p.Arg3047Ter) in exon 63 of 63 — a null variant in a gene where LOF is a known disease mechanism
- VCEP PVS1 document confirms p.R3047 is the most C-terminal pathogenic residue in ATM
- VCEP PVS1 document confirms all ATM exons are considered constitutive without major alternate splice isoforms
- PMID 21150274 demonstrates that R3047X protein is expressed but specifically deficient in oxidation-dependent ATM activation
- confirming functional significance despite potential NMD escape
Still missing
- The ATM PVS1 Decision Tree (pages 3-8 of ATM_PVS1_1.5.pdf) is image-based and could not be machine-read
- curator should confirm the exact decision path for a C-terminal nonsense variant at the boundary residue
- Extreme 3' end caveat applies — confirm whether full PVS1_VeryStrong is appropriate or whether downgrade to PVS1 (baseline) or PVS1_Strong is warranted given potential NMD escape at exon 63
Sources
Not met · 10 · evaluated, threshold not reached
PS3 No variant-specific functional data from VCEP-approved assays (kinase activity assay per Mitui 2009/Barone 2009/Scott 2002, or radiosensitivity assay) are available for c.9139C>T. Functional data in PMID 21150274 (Guo et al. 2010) demonstrates loss of oxidative activation in purified R3047X ATM protein, but this assay is not among the VCEP-approved functional assays listed in the clingen_hbop_atm_supplementary_tables_1_and_2_v1.xlsx. Details ▾Hide ▴
Evidence considered
- PMID 21150274: R3047X mutant protein can be activated by MRN/DNA but cannot be activated by oxidation in vitro
- Suppl Table S1 classifies c.9139C>T as Non-functional (combined score -2.075) based on in silico predictors
- not direct functional assay
Still missing
- No VCEP-approved kinase activity assay data for this variant
- No VCEP-approved radiosensitivity assay data for this variant
- Curator may consider whether the oxidative activation assay in PMID 21150274 could be accepted as an ATM-specific functional feature for PS3_Supporting
Sources
PS4 VCEP PS4 requires a case-control study with p≤0.05 AND (OR/HR/RR ≥2 OR lower 95% CI ≥1.5). No such case-control study was identified for c.9139C>T in the reviewed literature. Proband counting (PS4_Moderate) is not permitted under this VCEP. Details ▾Hide ▴
PM2 gnomAD v4.1 allele frequency is 1.61×10⁻⁵ (0.00161%, 26/1,613,988 alleles), which exceeds the VCEP PM2_Supporting threshold of ≤0.001% (≤1.0×10⁻⁵). The variant is present in gnomAD v2.1 at similar low frequency (1.77×10⁻⁵, 5/282,840 alleles). No homozygotes observed in either dataset. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: AF=1.61e-05 (0.00161%)
- grpmax FAF=4.37e-05
- gnomAD v2.1: AF=1.77e-05 (0.00177%)
- grpmax FAF=2.60e-05
- VCEP PM2 threshold: ≤0.001% in gnomAD v4
Still missing
- Overall AF of 0.00161% is only marginally above the 0.001% VCEP threshold
- Sub-population data for gnomAD v4.1 was not available
- if n=1 in a single sub-population
- PM2_Supporting would apply per VCEP instructions
Sources
PP1 PMID 19691550 (Chessa et al. 2009) reports two A-T families carrying c.9139C>T originating from Central Italy, confirming the variant is observed in A-T patients. However, the paper does not provide specific co-segregation data (number of affected relatives, genotypes of family members) that would allow application of PP1 under the VCEP framework, which requires segregation in 1, 2, or ≥3 affected relatives for the AR condition. Details ▾Hide ▴
Evidence considered
- PMID 19691550: 'Two families carrying the c.9139C>T mutation and two with c.4396C>T all originated from Central Italy'
Still missing
- No detailed co-segregation data (affected relatives count
- genotypes) available in reviewed sources
- Curator may have access to additional family data from the Italian A-T Registry
Sources
PP3 PP3 under the ATM VCEP applies to missense variants with REVEL >0.7333 or to splicing variants with SpliceAI ≥0.2. This is a nonsense variant; REVEL is not applicable. SpliceAI max delta score is 0.15 (<0.2 threshold). The BayesDel score of 0.617 does not have a defined VCEP PP3 threshold. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta: 0.15 (no predicted splice impact)
- REVEL: N/A for nonsense variant
- BayesDel: 0.617 (no VCEP PP3 threshold defined)
Sources
BA1 VCEP BA1 threshold is grpmax Filtering AF >0.5% in gnomAD v4. The observed grpmax FAF is 4.37×10⁻⁵ (0.00437%), far below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF: 4.37e-05 (0.00437%)
- VCEP BA1 threshold: >0.5%
Sources
BS1 VCEP BS1 threshold is grpmax Filtering AF >0.05% in gnomAD v4. The observed grpmax FAF is 4.37×10⁻⁵ (0.00437%), below the BS1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF: 4.37e-05 (0.00437%)
- VCEP BS1 threshold: >0.05%
Sources
BS3 No variant-specific benign functional data from VCEP-approved assays are available. The VCEP BS3_Moderate requires rescue of both an ATM-specific feature AND radiosensitivity; BS3_Supporting requires rescue of either. The available functional data (PMID 21150274) shows loss of oxidative activation, not rescue of normal function. Details ▾Hide ▴
Evidence considered
- PMID 21150274: R3047X shows loss of oxidation-dependent ATM activation
- not rescue of function
Sources
BP2 BP2 requires proband-level data (confirmed in trans with a pathogenic variant in unaffected individuals ≥18 years with no evidence of A-T) per the ATM PM3/BP2 table. No such proband data was available in the reviewed sources to calculate BP2 points. Details ▾Hide ▴
Still missing
- No proband-level phase/zygosity/phenotype data available to compute BP2 points
- Curator may have access to ClinGen variant curation interface data with specific proband entries
Sources
cspec ↗vcep_atm_pm3_bp2_1_5
BP4 BP4 under the ATM VCEP applies to missense variants with REVEL ≤0.249 or splicing variants with SpliceAI ≤0.1. This is a nonsense variant; REVEL is not applicable. SpliceAI max delta is 0.15 (>0.1 threshold), so the splicing-based BP4 is not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta: 0.15 (>0.1 BP4 threshold)
- REVEL: N/A for nonsense variant
Sources
Not applicable · 17· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 under the ATM VCEP is for missense changes at the same amino acid as a known pathogenic missense, or for splicing variants per the PS1 Splicing table. This variant is a nonsense substitution, not a missense change or a splicing variant. Details ▾Hide ▴
Sources
PS2 VCEPVCEP declares PS2 not applicable: de novo occurrences have not been observed for ATM-related conditions and phase cannot be reliably determined for autosomal recessive disorders. Details ▾Hide ▴
Sources
PM1 VCEPVCEP declares PM1 not applicable for ATM: benign and pathogenic variants are known to occur within the same domains and germline mutational hotspots are not well defined. Details ▾Hide ▴
Sources
PM3 N/ASKIP — trivially not applicable; PM3 requires detection in trans with a pathogenic variant, which requires proband-level phase data not assessed here. Details ▾Hide ▴
No further detail was recorded.
PM4 N/ASKIP — trivially not applicable; variant is a substitution, not a protein-length-altering in-frame deletion/insertion or stop-loss. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AThe VCEP PM5 rule applies to frameshifting or truncating variants with premature termination codons upstream of p.Arg3047. This variant creates a termination codon at exactly p.Arg3047 (the defined C-terminal boundary), not upstream of it. The variant itself — p.Arg3047Ter — is cited by the VCEP as the most C-terminal known pathogenic variant and defines the PM5 boundary rather than falling within its scope. Details ▾Hide ▴
Evidence considered
- VCEP PM5 boundary: p.Arg3047*
- This variant: p.Arg3047Ter (at the boundary
- not upstream)
Sources
cspec ↗pm5_candidates
PM6 VCEPVCEP declares PM6 not applicable: informative de novo occurrences have not been observed for ATM-related conditions and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
Sources
PP2 VCEPVCEP declares PP2 not applicable: ATM does not have a defined low rate of missense benign variation. Details ▾Hide ▴
Sources
PP4 VCEPVCEP declares PP4 not applicable: for autosomal dominant, breast cancer has multiple genetic etiologies; for autosomal recessive, such evidence is built into the A-T PM3/BP2 table. Details ▾Hide ▴
Sources
BS2 VCEPVCEP declares BS2 not applicable: ATM has incomplete penetrance. Details ▾Hide ▴
Sources
BS4 VCEPVCEP declares BS4 not applicable: informative instances of lack of co-segregation in A-T families are too rare to be considered for weight, and biallelic unaffected patients can be considered under BP2 instead. Details ▾Hide ▴
Sources
BP1 VCEPVCEP declares BP1 not applicable: missense pathogenic variants are known for ATM, so the premise that primarily truncating variants cause disease does not hold. Details ▾Hide ▴
Sources
BP3 VCEPVariant is a substitution, not an in-frame deletion/insertion in a repetitive region. Details ▾Hide ▴
No further detail was recorded.
BP5 VCEPVCEP declares BP5 not applicable: cases with multiple pathogenic variants have been observed with no noticeable phenotype difference, and ATM has low penetrance, making co-occurrence of pathogenic variants uninformative. Details ▾Hide ▴
Sources
BP6 VCEPVCEP declares BP6 not applicable: this criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Sources
BP7 N/ABP7 applies to synonymous and deep intronic variants. This variant is a nonsense substitution (c.9139C>T, p.Arg3047Ter), not a synonymous or intronic change. Details ▾Hide ▴
Sources
PS5 N/APS5 is not recognized as a standalone criterion by the HBOP VCEP v1.5.0 for ATM. The original ACMG PS5 (same criterion as PS4 but at lower statistical threshold) is not included in the VCEP criteria set. Details ▾Hide ▴
Sources
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.9139C>T
- Protein (HGVS p.)
- NP_000042.3:p.(Arg3047Ter)
- GRCh38
- chr11:108365476 C>T
- GRCh37
- chr11:108236203 C>T
- ClinVar
- 3029, 557378
- COSMIC
- COSV53724126
Gene diagram
Every interpreted variant in ATM, mapped onto the exon structure of NM_000051.4. Select a row to find it on the plot.
ATMNM_000051.4
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in ATM
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
26 / 1,613,988 alleles
AF 1.61e-05 · 0 homozygotes · FAF 4.37e-05
gnomAD v2.1
5 / 282,840 alleles
AF 1.77e-05 · 0 homozygotes · FAF 2.6e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.6e-05 · 26 / 1,613,988 alleles · 0 hom · FAF 4.4e-05
| South Asian8 / 91,078 | 8.8e-05 |
| European (Finnish)2 / 64,002 | 3.1e-05 |
| African/African American1 / 74,912 | 1.3e-05 |
| European (non-Finnish)15 / 1,180,030 | 1.3e-05 |
0 alternate alleles recorded in 6 other groups: Remaining individuals, Admixed American, Amish, East Asian, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 1.8e-05 · 5 / 282,840 alleles · 0 hom · FAF 2.6e-05
| South Asian3 / 30,610 | 9.8e-05 |
| European (Finnish)1 / 25,120 | 4e-05 |
| European (non-Finnish)1 / 129,174 | 7.7e-06 |
0 alternate alleles recorded in 5 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.61092e-05; MAF= 0.00161%, 26/1613988 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 8.78368e-05; MAF= 0.00878%, 8/91078 alleles, homozygotes = 0); grpmax FAF= 4.368e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.76778e-05; MAF= 0.00177%, 5/282840 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 9.80072e-05; MAF= 0.00980%, 3/30610 alleles, homozygotes = 0); grpmax FAF= 2.596e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- 0.617
How the predictions were used
PP3 PP3 under the ATM VCEP applies to missense variants with REVEL >0.7333 or to splicing variants with SpliceAI ≥0.2. This is a nonsense variant; REVEL is not applicable. SpliceAI max delta score is 0.15 (<0.2 threshold). The BayesDel score of 0.617 does not have a defined VCEP PP3 threshold. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta: 0.15 (no predicted splice impact)
- REVEL: N/A for nonsense variant
- BayesDel: 0.617 (no VCEP PP3 threshold defined)
Sources
BP4 BP4 under the ATM VCEP applies to missense variants with REVEL ≤0.249 or splicing variants with SpliceAI ≤0.1. This is a nonsense variant; REVEL is not applicable. SpliceAI max delta is 0.15 (>0.1 threshold), so the splicing-based BP4 is not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta: 0.15 (>0.1 BP4 threshold)
- REVEL: N/A for nonsense variant
Sources
BP7 N/ABP7 applies to synonymous and deep intronic variants. This variant is a nonsense substitution (c.9139C>T, p.Arg3047Ter), not a synonymous or intronic change. Details ▾Hide ▴
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.15). BayesDel score = 0.61701.
7 paper records listed. 2 cited in the classification.
Cited in the classification
-
PMID 19691550 ↗Founder effects for ATM gene mutations in Italian Ataxia Telangiectasia families.Chessa L et al. · 2009 SepTwo Italian A-T families from Central Italy carried the c.9139C>T mutation. Haplotype analysis was performed across 48 A-T families with 16 recurrent mutations, including c.9139C>T. The variant was identified as one of several recurrent ATM mutations with founder effects in the Italian population.→ PVS1 Names this variant
Source detail
Two families carrying the c.9139C>T mutation and two with c.4396C>T all originated from Central Italy.
Location Results section, line 235-236
Context Mutation screening (DHPLC, PTT, SSCP, HA, REF) of 104 Italian A-T patients from 91 families; haplotype analysis with 5 microsatellite markers.
-
PMID 21150274 ↗ATM activation in the presence of oxidative stress.Guo Z et al. · 2010 Dec 15The R3047X mutant ATM protein (lacking the C-terminal 10 amino acids) can be fully activated by MRN and DNA but cannot be activated by oxidation in vitro. Cells from an A-T patient expressing R3047X were specifically deficient in oxidative activation of ATM but showed normal ATM activation in response to DNA damage, with only moderate radiosensitivity. The variant is described as a causative mutation in several A-T patients, sometimes classified as A-T variants due to milder phenotype.→ PVS1 Names this variant
Source detail
a mutant lacking the last ten amino acids of the ATM C-terminus results in a mutant protein (R3047X, Fig. 1A) that can be fully activated by MRN and DNA but cannot be activated by oxidation in vitro.
Location Results section; Figure 1A
Context In vitro kinase assays with purified ATM wild-type and mutant proteins; phosphorylation of GST-p53 substrate assessed by western blotting. Patient-derived cells used for cellular validation.
Other recorded publications
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PMID 19431188 ↗Modeling ATM mutant proteins from missense changes confirms retained kinase activity.No paper-specific finding is recorded.
-
PMID 10980530 ↗Characterization of ATM mutations in 41 Nordic families with ataxia telangiectasia.No paper-specific finding is recorded.
-
PMID 18560558 ↗Critical involvement of the ATM-dependent DNA damage response in the apoptotic demise of HIV-1-elicited syncytia.Perfettini JL et al. · 2008Discusses ATM-dependent DNA damage response in HIV-1-elicited syncytia. NM_000051.4:c.9139C>T was not identified in this paper.Does not name this variant
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PMID 22649200 ↗Classical ataxia telangiectasia patients have a congenitally aged immune system with high expression of CD95.Carney EF et al. · 2012No paper-specific finding is recorded.
-
PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.ACMG/AMP standards and guidelines for variant interpretation. NM_000051.4:c.9139C>T was not identified in this paper.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
26 / 1,613,988 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.150
Open source ↗
ClinVar
18 Pathogenic
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/639508985
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/3029/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108236203-C-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108365476-C-T?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/11-108365476-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.9139…
- OncoKB ↗www.oncokb.org/gene/ATM/R3047*
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=122703484
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.61092e-05; MAF= 0.00161%, 26/1613988 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 8.78368e-05; MAF= 0.00878%, 8/91078 alleles, homozygotes = 0); grpmax FAF= 4.368e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.76778e-05; MAF= 0.00177%, 5/282840 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 9.80072e-05; MAF= 0.00980%, 3/30610 alleles, homozygotes = 0); grpmax FAF= 2.596e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Pathogenic (18 clinical laboratories) and as Pathogenic by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 3029)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.15). BayesDel score = 0.61701.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV53724126, n = 18 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.