About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.7913G>A, p.(Trp2638Ter)
Classification
Pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A pathogenic classification under the recorded framework.
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. 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: 3
Benign evidence criteria: 0
Pathogenic criteria applied · 3
PVS1Very strong
PVS1 · very strong
NM_000051.4:c.7913G>A is a nonsense variant producing a premature termination codon at p.Trp2638 in exon 53 of ATM. Loss of function is a well-established disease mechanism for ATM, and the HBOP VCEP PVS1 decision tree supports application of PVS1 at very strong strength for this variant. The PTC is upstream of p.Arg3047 (the most C-terminal known pathogenic variant), and NMD is expected.
PM2Supporting
PM2 · supporting
c.7913G>A is present at extremely low frequency in gnomAD v4.1 (allele frequency = 0.00074%, 12/1,612,586 alleles, 0 homozygotes; grpmax FAF = 0.007%). This is well below the VCEP threshold of ≤0.001% for PM2_Supporting.
PM5Supporting
PM5 · supporting
c.7913G>A produces a premature termination codon at p.Trp2638, which is upstream of p.Arg3047 — the most C-terminal known pathogenic variant in ATM. PM5_Supporting applied per VCEP truncation cutoff rule for frameshifting or truncating variants with PTCs upstream of p.Arg3047.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Pathogenic
ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ATM Version 1.5 v1.5 criteria-combination framework: matched Rule4 (1 Pathogenic.Very Strong + Pathogenic.Supporting >=2) with applied criteria: PVS1 very strong, PM2 supporting, PM5 supporting; maps to Pathogenic.
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
12 / 1,612,586 alleles
gnomAD v4.1: 12 / 1,612,586 alleles. Recorded AF 7.44146e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.77475e-05; MAF= 0.00177%, 5/281730 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000160372; MAF= 0.01604%, 4/24942 alleles, homozygotes = 0); grpmax FAF= 9.374e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
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
21 reported laboratory submissions
19 Pathogenic · 1 Likely pathogenic · 1 pathogenic. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
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
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
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, with the data and sources behind each one.
26 criteria with recorded statuses: 3 met · 8 not met · 1 not assessed · 14 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.7913G>A is a nonsense variant (p.Trp2638Ter) in exon 53 of ATM, a gene for which loss of function is a well-established mechanism of disease. The premature termination codon is upstream of p.Arg3047, and NMD is expected. PVS1 is applied at very strong strength per the ClinGen HBOP VCEP ATM PVS1 decision tree.
This variant is present at extremely low frequency in gnomAD v4.1 (AF = 0.00074%, 12/1,612,586 alleles, 0 homozygotes; grpmax FAF = 0.007%), meeting the VCEP PM2_Supporting threshold of ≤0.001%.
The variant produces a premature termination codon at p.Trp2638, upstream of the most C-terminal known pathogenic variant p.Arg3047, satisfying the VCEP PM5_Supporting truncation cutoff rule.
This variant has been observed in the literature in multiple unrelated AT patients: as a compound heterozygous mutation (with c.3802delG) in Brazilian AT patients (Coutinho et al. 2004, PMID:15039971), as a homozygous mutation in a consanguineous African-Brazilian patient with classical AT (Demuth et al. 2011, PMID:21965147), and as a homozygous mutation in an AT proband (Family 605) studied for gamma-H2AX radiosensitivity (Kato et al. 2006, PMID:16953663). These observations are consistent with biallelic pathogenicity for ataxia telangiectasia.
The VCEP combination rule 4 is satisfied: 1 Very Strong criterion (PVS1) + ≥2 Supporting criteria (PM2_Supporting, PM5_Supporting) → Pathogenic classification.
No criteria match.
Met · 3
PVS1 Very strongNM_000051.4:c.7913G>A is a nonsense variant producing a premature termination codon at p.Trp2638 in exon 53 of ATM. Loss of function is a well-established disease mechanism for ATM, and the HBOP VCEP PVS1 decision tree supports application of PVS1 at very strong strength for this variant. The PTC is upstream of p.Arg3047 (the most C-terminal known pathogenic variant), and NMD is expected. Details ▾Hide ▴
Evidence considered
- Nonsense variant (p.Trp2638Ter) in exon 53 of ATM
- LOF is established disease mechanism for ATM per ClinGen HBOP VCEP
- PTC at codon 2638 is upstream of most C-terminal pathogenic variant p.Arg3047
- NMD expected — variant is not in the extreme 3' region
- ATM PVS1 decision tree (VCEP v1.5) supports PVS1_VeryStrong
Sources
PM2 Supportingc.7913G>A is present at extremely low frequency in gnomAD v4.1 (allele frequency = 0.00074%, 12/1,612,586 alleles, 0 homozygotes; grpmax FAF = 0.007%). This is well below the VCEP threshold of ≤0.001% for PM2_Supporting. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF = 7.44e-06 (0.00074%)
- 12/1
- 612
- 586 alleles
- 0 homozygotes
- grpmax FAF = 7.23e-05 (0.007%)
- Meets VCEP PM2_Supporting threshold (≤0.001%)
Sources
PM5 Supportingc.7913G>A produces a premature termination codon at p.Trp2638, which is upstream of p.Arg3047 — the most C-terminal known pathogenic variant in ATM. PM5_Supporting applied per VCEP truncation cutoff rule for frameshifting or truncating variants with PTCs upstream of p.Arg3047. Details ▾Hide ▴
Evidence considered
- Nonsense variant produces PTC at p.Trp2638
- Most C-terminal known pathogenic variant: p.Arg3047
- PTC is upstream of cutoff — PM5_Supporting applies per VCEP
Sources
cspec ↗pm5_candidates
Not met · 8 · evaluated, threshold not reached
PS3 No variant-specific experimental functional rescue data (ATM-specific kinase activity or radiosensitivity rescue) is available for c.7913G>A. The VCEP Suppl Table S1 (PMID:40580951) classifies this variant as Non-functional (High confidence) via computational prediction, but this is in silico evidence — the VCEP PS3 rule requires experimental rescue assay data (failure to rescue ATM-specific phosphorylation targets and/or radiosensitivity). Computational predictions do not independently satisfy the VCEP PS3 requirement. Details ▾Hide ▴
Evidence considered
- VCEP Suppl Table S1 classifies c.7913G>A as Non-functional (High confidence
- Combined_score: -3.949)
- No experimental rescue assay (kinase activity or radiosensitivity) identified for this variant
- VCEP PS3 rule requires failure to rescue both ATM-specific feature AND radiosensitivity (moderate) or ATM-specific feature only (supporting)
Still missing
- No experimental functional rescue assay data available for c.7913G>A
Sources
vcep_suppl_tables1_pmid_40580951cspec ↗
PS4 No case-control study with p-value ≤0.05 and OR ≥2 (or lower 95% CI ≥1.5) is available for this variant. The ATM VCEP restricts PS4 to formal case-control studies meeting these statistical thresholds. Details ▾Hide ▴
PP1 No co-segregation data in affected relatives is available for assessment. PP1 under the ATM VCEP requires documented segregation in AR-affected relatives carrying both variants identified in the proband. Details ▾Hide ▴
PP3 PP3 under the ATM VCEP applies to missense variants with REVEL >0.7333 or splicing variants with SpliceAI ≥0.2. c.7913G>A is a nonsense variant with no REVEL score available, and SpliceAI max delta score is 0.15 (below the 0.2 threshold). The VCEP PP3 rule does not cover nonsense variants. Details ▾Hide ▴
Evidence considered
- Nonsense variant — no REVEL score applicable
- SpliceAI max delta = 0.15 (below 0.2 VCEP threshold)
Sources
BA1 gnomAD v4.1 grpmax filtering AF is 7.23e-05 (0.007%), well below the VCEP BA1 threshold of >0.5%. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 7.23e-05 (0.007%)
- VCEP BA1 threshold: >0.5% — not met
Sources
BS1 gnomAD v4.1 grpmax filtering AF is 7.23e-05 (0.007%), well below the VCEP BS1 threshold of >0.05%. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 7.23e-05 (0.007%)
- VCEP BS1 threshold: >0.05% — not met
Sources
BS3 No experimental evidence that c.7913G>A rescues ATM-specific function (kinase activity) or radiosensitivity. The VCEP BS3 rule requires rescue of both ATM-specific features and radiosensitivity (moderate) or either (supporting). The VCEP functional reference tables do not list this variant as having rescue data. Details ▾Hide ▴
BP4 BP4 under the ATM VCEP applies to missense variants with REVEL ≤0.249 or splicing variants with SpliceAI ≤0.1. c.7913G>A is a nonsense variant with no REVEL score, and SpliceAI max delta is 0.15 (above the 0.1 BP4 threshold). Neither condition is met. Details ▾Hide ▴
Evidence considered
- Nonsense variant — REVEL score not applicable
- SpliceAI max delta = 0.15 (above 0.1 BP4 threshold)
Sources
Not assessed · 1 · no assessment recorded
BP2 No proband data with trans observations in unaffected individuals is available to assign BP2 points per the ATM PM3/BP2 table. Details ▾Hide ▴
Not applicable · 14· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 applies to missense changes under the ATM VCEP. NM_000051.4:c.7913G>A is a nonsense variant, not a missense substitution. Details ▾Hide ▴
No further detail was recorded.
PS2 VCEPNot applicable per the ATM HBOP VCEP v1.5: informative de novo occurrences have not been observed for ATM-related disorders, and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
Sources
PM1 VCEPNot applicable per the ATM HBOP VCEP v1.5: benign and pathogenic variants are known to occur within the same domains, and germline mutational hotspots are not well defined for ATM at this time. Details ▾Hide ▴
Sources
PM6 VCEPNot applicable per the ATM HBOP VCEP v1.5: informative de novo occurrences have not been observed for ATM-related disorders, and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
Sources
PP2 VCEPNot applicable per the ATM HBOP VCEP v1.5: ATM does not have a defined low rate of benign missense variation. Details ▾Hide ▴
Sources
PP4 VCEPNot applicable per the ATM HBOP VCEP v1.5: for AD, breast cancer has multiple genetic etiologies with no distinguishing features from sporadic causes; for AR, phenotype evidence is built into the PM3/BP2 table. Details ▾Hide ▴
Sources
PP5 VCEPNot applicable per the ATM HBOP VCEP v1.5: this criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Sources
BS2 VCEPNot applicable per the ATM HBOP VCEP v1.5: ATM has incomplete penetrance, precluding use of BS2. Details ▾Hide ▴
Sources
BS4 VCEPNot applicable per the ATM HBOP VCEP v1.5: informative lack of co-segregation in A-T families is too rare to be weighted, and co-segregation analysis in low-penetrance genes can yield false positives. Details ▾Hide ▴
Sources
BP1 VCEPNot applicable per the ATM HBOP VCEP v1.5: missense pathogenic variants are known for ATM. Details ▾Hide ▴
Sources
BP5 VCEPNot applicable per the ATM HBOP VCEP v1.5: cases with multiple pathogenic variants have been observed with no noticeable phenotype difference, and ATM has low penetrance making co-occurrence with other pathogenic variants more frequent in the general population. Details ▾Hide ▴
Sources
BP6 VCEPNot applicable per the ATM HBOP VCEP v1.5: this criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Sources
BP7 N/ABP7 under the ATM VCEP applies to synonymous and deep intronic variants only. c.7913G>A is a nonsense variant. Details ▾Hide ▴
Sources
PS5 N/APS5 is not a defined criterion in the ATM HBOP VCEP v1.5 framework. The VCEP does not provide specifications for PS5; the semantics of same-residue pathogenic change for truncating variants are handled under PM5. Details ▾Hide ▴
Sources
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.7913G>A
- Protein (HGVS p.)
- NP_000042.3:p.(Trp2638Ter)
- GRCh38
- chr11:108332886 G>A
- GRCh37
- chr11:108203613 G>A
- ClinVar
- 141233, 626061, 127414
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
12 / 1,612,586 alleles
AF 7.44e-06 · 0 homozygotes · FAF 7.23e-05
gnomAD v2.1
5 / 281,730 alleles
AF 1.77e-05 · 0 homozygotes · FAF 9.37e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 7.4e-06 · 12 / 1,612,586 alleles · 0 hom · FAF 7.2e-05
| African/African American10 / 74,904 | 0.00013 |
| Admixed American1 / 59,992 | 1.7e-05 |
| Remaining individuals1 / 62,444 | 1.6e-05 |
0 alternate alleles recorded in 7 other groups: European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, European (non-Finnish).
gnomAD v2.1
AF 1.8e-05 · 5 / 281,730 alleles · 0 hom · FAF 9.4e-05
| African/African American4 / 24,942 | 0.00016 |
| Remaining individuals1 / 7,202 | 0.00014 |
0 alternate alleles recorded in 6 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 7.44146e-06; MAF= 0.00074%, 12/1612586 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000133504; MAF= 0.01335%, 10/74904 alleles, homozygotes = 0); grpmax FAF= 7.23e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.77475e-05; MAF= 0.00177%, 5/281730 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000160372; MAF= 0.01604%, 4/24942 alleles, homozygotes = 0); grpmax FAF= 9.374e-05.
gnomAD-Canada
Absent from 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 splicing variants with SpliceAI ≥0.2. c.7913G>A is a nonsense variant with no REVEL score available, and SpliceAI max delta score is 0.15 (below the 0.2 threshold). The VCEP PP3 rule does not cover nonsense variants. Details ▾Hide ▴
Evidence considered
- Nonsense variant — no REVEL score applicable
- SpliceAI max delta = 0.15 (below 0.2 VCEP threshold)
Sources
BP4 BP4 under the ATM VCEP applies to missense variants with REVEL ≤0.249 or splicing variants with SpliceAI ≤0.1. c.7913G>A is a nonsense variant with no REVEL score, and SpliceAI max delta is 0.15 (above the 0.1 BP4 threshold). Neither condition is met. Details ▾Hide ▴
Evidence considered
- Nonsense variant — REVEL score not applicable
- SpliceAI max delta = 0.15 (above 0.1 BP4 threshold)
Sources
BP7 N/ABP7 under the ATM VCEP applies to synonymous and deep intronic variants only. c.7913G>A is a nonsense variant. Details ▾Hide ▴
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.15). BayesDel score = 0.61701.
8 paper records listed. 3 cited in the classification.
Cited in the classification
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PMID 15039971 ↗Five haplotypes account for fifty-five percent of ATM mutations in Brazilian patients with ataxia telangiectasia: seven new mutations.Coutinho G et al. · 2004 Apr 17913G>A (nonsense, p.Trp2638Ter) identified as a recurring founder mutation on haplotype [I] in three unrelated Brazilian AT patients (BRAT12-3, BRAT15-3, BRAT30-3), each compound heterozygous with c.3802delG. The mutation introduces a premature termination codon and was detected by SSCP after PTT failed to show a truncated band. Associated with the classical AT phenotype.→ PVS1 → PM5 Names this variant
Source detail
The mutation 7913G > A, associated with the recurring haplotype [I], introduces a premature termination codon.
Location Table I (genotype/haplotype correlation table); Results, paragraph on mutations; Discussion, paragraph on founder mutations
Context Protein truncation testing (PTT), SSCP, dHPLC mutation screening in 27 Brazilian AT families; lymphoblastoid cell lines
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PMID 16953663 ↗Levels of gamma-H2AX Foci after low-dose-rate irradiation reveal a DNA DSB rejoining defect in cells from human ATM heterozygotes in two at families and in another apparently normal individual.Kato TA et al. · 2006 SepFamily 605 proband is homozygous for the 7913G>A substitution. Both obligate heterozygous parents carry the same G>A substitution at nucleotide 7913. All three siblings were confirmed heterozygous. The study measured gamma-H2AX foci after low-dose-rate irradiation and demonstrated a DNA DSB rejoining defect in ATM heterozygotes from this family, confirming the functional impact of this variant on DNA damage response.→ PVS1 Names this variant
Source detail
The proband in family 605 is homozygous for a 7913G>A mutation.
Location Materials and Methods, Genotyping section; Results, Table 1 footnote; Discussion, sibling genotyping results
Context gamma-H2AX focus assay in primary fibroblasts after low-dose-rate (10 cGy/h) and acute (1 Gy) irradiation; Coriell cell strains from Family 605
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PMID 21965147 ↗New mutations in the ATM gene and clinical data of 25 AT patients.Demuth I et al. · 2011 Novc.7913G>A (p.W2638X) identified in two AT patients: patient 15227 (Portuguese, compound heterozygous with c.3994-1413del3450) and patient 15106 (African-Brazilian, homozygous, consanguineous, classical AT phenotype with ataxia onset at 18 months, telangiectasia, choreoathetosis, infections, and elevated AFP).→ PVS1 → PM5 Names this variant
Source detail
c.7913G>A / p.W2638X
Location Table 2 (mutation list); Table 3 (clinical data for patient 15106)
Context Western blot for ATM protein, p53 phosphorylation after IR, cell cycle analysis in lymphoblastoid cell lines
Other recorded publications
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PMID 27413114 ↗ATM Mutations in Cancer: Therapeutic Implications.Review article on ATM mutations in cancer and therapeutic implications. The specific variant NM_000051.4:c.7913G>A was not identified in the abstract. Full text not available.Does not name this variant
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PMID 30348496 ↗Inactive Atm abrogates DSB repair in mouse cerebellum more than does Atm loss, without causing a neurological phenotype.Investigates the effects of ATM kinase-dead vs ATM-null mutations in a mouse model, demonstrating that ATM kinase inactivation causes more severe cerebellar DSB repair defects than ATM loss. The human variant NM_000051.4:c.7913G>A was not identified in this paper.Does not name this variant
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PMID 30553448 ↗Loss of ATM positively regulates Rac1 activity and cellular migration through oxidative stress.Demonstrates that loss of ATM elevates intracellular ROS leading to Rac1 activation and increased cellular migration. Uses ATM knockdown/knockout models. The specific variant NM_000051.4:c.7913G>A was not identified in this paper.Does not name this variant
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PMID 12815592 ↗Independent mutational events are rare in the ATM gene: haplotype prescreening enhances mutation detection rate.Mitui M et al. · 2003Describes STR haplotype prescreening to enhance ATM mutation detection in 55 Iberian AT families. NM_000051.4:c.7913G>A was not identified in the abstract; full text not available for confirmation.Does not name this variant
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PMID 23807571 ↗Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients.Huang Y et al. · 2013Reports twelve novel ATM mutations in Chinese AT patients. The variant NM_000051.4:c.7913G>A was not identified among the mutations reported 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
12 / 1,612,586 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
19 Pathogenic · 1 Likely pathogenic · 1 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/141233/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108203613-G-A?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108332886-G-A?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/11-108332886-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.7913…
- OncoKB ↗www.oncokb.org/gene/ATM/W2638*
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=ATM+c.7913G%3EA
- 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= 7.44146e-06; MAF= 0.00074%, 12/1612586 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000133504; MAF= 0.01335%, 10/74904 alleles, homozygotes = 0); grpmax FAF= 7.23e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.77475e-05; MAF= 0.00177%, 5/281730 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000160372; MAF= 0.01604%, 4/24942 alleles, homozygotes = 0); grpmax FAF= 9.374e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Pathogenic (19 clinical laboratories) and as Likely pathogenic (1 clinical laboratory) and as pathogenic (1 clinical laboratory). (ClinVarID = 141233)
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 not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.