About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.2413C>T, p.(Arg805Ter)
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 v1.5.0. 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: 3
Benign evidence criteria: 0
Pathogenic criteria applied · 3
PVS1Very strong
PVS1 · very strong
This nonsense variant introduces a premature stop codon at p.Arg805Ter (p.R805*), well upstream of the 3' end of ATM, and ATM loss of function is an established disease mechanism in the ATM HBOP expert-panel framework. Available ATM-specific PVS1 guidance therefore supports full-strength PVS1 for this early truncating variant.
PM5Supporting
PM5 · supporting
The ATM HBOP specification permits PM5 at supporting strength for truncating variants with premature termination codons upstream of p.Arg3047. This variant creates p.Arg805Ter, which is far upstream of p.Arg3047, so PM5_Supporting is met under the ATM-specific rule.
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: Pathogenic
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework: matched Rule4 (1 Pathogenic.Very Strong + Pathogenic.Supporting >=2) with applied criteria: PVS1 very strong, PM5 supporting, PP5 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
13 / 1,613,688 alleles
gnomAD v4.1: 13 / 1,613,688 alleles. Recorded AF 8.05608e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.98067e-05; MAF= 0.00398%, 10/251214 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.0003263; MAF= 0.03263%, 6/18388 alleles, homozygotes = 0); grpmax FAF= 0.00014149.
No listed criterion applied
SpliceAI score
0.180 maximum delta
Recorded SpliceAI maximum delta score: 0.180. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
17 reported laboratory submissions
17 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
11 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV53736642, n = 11 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.
28 criteria with recorded statuses: 3 met · 4 not met · 5 not assessed · 16 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The ATM c.2413C>T (p.Arg805Ter; p.R805*) variant has been reported in ClinVar as Pathogenic by the ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel and is also cataloged in a cancer knowledgebase with variant-specific somatic context.
This variant is present in gnomAD v4.1 at an overall allele frequency of 0.00081% (13/1613688) with a highest observed East Asian frequency of 0.00669% (3/44820); these values are below the ATM BS1 and BA1 thresholds but the East Asian frequency is above the ATM PM2_Supporting threshold of 0.001%.
Curated literature resources identify this variant in an ATM loss-of-function context, but no ATM-specific functional rescue data were confirmed here that meet the expert-panel requirements for PS3 or BS3.
This variant introduces a premature termination codon at Arg805, well upstream of the ATM truncation cutoff used by the expert panel, which supports PVS1 and PM5_Supporting under the ATM-specific rules; REVEL was unavailable, BayesDel was 0.588046, and no SpliceAI-based evidence was captured for a splice-specific computational call.
No criteria match.
Met · 3
PVS1 Very strongThis nonsense variant introduces a premature stop codon at p.Arg805Ter (p.R805*), well upstream of the 3' end of ATM, and ATM loss of function is an established disease mechanism in the ATM HBOP expert-panel framework. Available ATM-specific PVS1 guidance therefore supports full-strength PVS1 for this early truncating variant. Details ▾Hide ▴
Rule
ATM VCEP PVS1 decision tree for truncating variants in a gene with established loss-of-function mechanism
Evidence considered
- Protein consequence p.Arg805Ter (p.R805*)
- ATM VCEP/HBOP framework includes gene-specific PVS1 guidance
- Variant is an early nonsense change rather than a distal 3' truncation
Sources
PM5 SupportingThe ATM HBOP specification permits PM5 at supporting strength for truncating variants with premature termination codons upstream of p.Arg3047. This variant creates p.Arg805Ter, which is far upstream of p.Arg3047, so PM5_Supporting is met under the ATM-specific rule. Details ▾Hide ▴
Rule
ATM PM5_Supporting for truncating variants upstream of p.Arg3047
Evidence considered
- ATM PM5 truncation-cutoff rule
- Premature stop at codon 805 is upstream of codon 3047
Sources
cspec ↗pm5_candidates
PP5 SupportingExpert panel ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen classified as Pathogenic. Details ▾Hide ▴
Not met · 4 · evaluated, threshold not reached
PS4 This variant has been reported in affected individuals and is classified as Pathogenic in ClinVar, but no case-control study or other enrichment analysis meeting the ATM PS4 requirement of p-value 0.05 or less with an effect estimate of at least 2 was identified. Available evidence does not support PS4. Details ▾Hide ▴
Rule
ATM PS4 requires qualifying case-control enrichment evidence
Evidence considered
- ClinVar expert-panel pathogenic classification
- Reported literature does not provide qualifying case-control statistics
Sources
PM2 This variant is rare overall in gnomAD v4.1 at 13/1613688 alleles (0.00081%), but the highest observed subpopulation frequency is 3/44820 East Asian alleles (0.00669%), which is above the ATM PM2_Supporting threshold of 0.001%. Available population data therefore do not support PM2. Details ▾Hide ▴
Rule
ATM PM2_Supporting: frequency <=0.001% in gnomAD v4 dataset
Evidence considered
- gnomAD v4.1 total AF 0.00081%
- gnomAD v4.1 East Asian AF 0.00669%
- ATM PM2 threshold 0.001%
Sources
BA1 The highest gnomAD v4.1 filtering allele frequency is 0.001775%, which is below the ATM BA1 threshold of greater than 0.5%. Population data do not support BA1. Details ▾Hide ▴
Rule
ATM BA1 uses gnomAD v4 grpmax filtering AF >0.5%
Evidence considered
- gnomAD v4.1 grpmax FAF 0.001775%
- ATM BA1 threshold >0.5%
Sources
BS1 The highest gnomAD v4.1 filtering allele frequency is 0.001775%, which is below the ATM BS1 threshold of greater than 0.05%. Population data do not support BS1. Details ▾Hide ▴
Rule
ATM BS1 uses gnomAD v4 grpmax filtering AF >0.05%
Evidence considered
- gnomAD v4.1 grpmax FAF 0.001775%
- ATM BS1 threshold >0.05%
Sources
Not assessed · 5 · no assessment recorded
PS3 Curated literature resources identified functional publications relevant to ATM loss of function, but no assay result was confirmed here showing that this exact variant failed to rescue both an ATM-specific feature and radiosensitivity, as required for ATM PS3. Available evidence is therefore insufficient to apply PS3. Details ▾Hide ▴
Rule
ATM PS3 Moderate/Supporting rescue-failure framework
Evidence considered
- OncoKB flags variant-specific curated literature and loss-of-function context
- ATM PS3 requires validated ATM-specific functional rescue failure criteria
Still missing
- Direct review of variant-specific ATM functional rescue data would be needed to determine PS3 eligibility.
Sources
PM3 No proband-level phase data were identified showing this variant in trans with a pathogenic ATM variant in an individual with ataxia-telangiectasia. Available evidence is insufficient to assign PM3 points. Details ▾Hide ▴
Rule
ATM PM3 point-based recessive framework
Evidence considered
- No qualifying trans observations documented in the reviewed sources
Still missing
- Confirmed phase and phenotype details would be needed for PM3 point assignment.
Sources
vcep_atm_pm3_bp2_1_5cspec ↗
PP1 No segregation data were identified showing this variant tracking with disease in affected relatives. Available evidence is insufficient to apply PP1. Details ▾Hide ▴
Rule
ATM PP1 segregation thresholds for recessive disease
Evidence considered
- No qualifying segregation counts identified
Still missing
- Family-level segregation data would be needed to assess PP1.
Sources
BS3 Curated literature resources identified functional publications relevant to ATM, but no confirmed assay result was identified here showing rescue of both an ATM-specific feature and radiosensitivity, or rescue of either feature alone, as required for ATM BS3. Available evidence is insufficient to apply BS3. Details ▾Hide ▴
Rule
ATM BS3 Moderate/Supporting rescue framework
Evidence considered
- OncoKB flags variant-specific curated literature and loss-of-function context
- ATM BS3 requires validated rescue evidence
Still missing
- Direct review of variant-specific ATM rescue data would be needed to determine BS3 eligibility.
Sources
BP2 No confirmed co-occurrence data were identified showing this variant in trans with a pathogenic ATM variant in an unaffected non-ataxia-telangiectasia individual, or in another qualifying benign co-occurrence setting. Available evidence is insufficient to assign BP2 points. Details ▾Hide ▴
Rule
ATM BP2 point-based co-occurrence framework
Evidence considered
- No qualifying benign co-occurrence observations documented in the reviewed sources
Still missing
- Qualifying co-occurrence and phenotype information would be needed for BP2 point assignment.
Sources
vcep_atm_pm3_bp2_1_5cspec ↗
Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/AThis variant is a nonsense change and no same-effect splice comparator evidence was identified. The ATM PS1 specification is directed to missense substitutions or splice variants with matched predicted or observed splice effects, so PS1 is not applicable here. Details ▾Hide ▴
Rule
ATM PS1 specification for missense or matched splice events
Evidence considered
- Variant consequence is p.Arg805Ter (nonsense)
- No qualifying splice comparator evidence identified
Sources
cspec ↗vcep_atm_ps1_1_5
PS2 VCEPThe ATM HBOP specification lists PS2 as not applicable for this gene-disease framework. Details ▾Hide ▴
VCEP rule
ATM HBOP specification
Evidence considered
- ATM HBOP criteria table marks PS2 not applicable
Sources
PM1 VCEPThe ATM HBOP specification lists PM1 as not applicable for this gene-disease framework. Details ▾Hide ▴
VCEP rule
ATM HBOP specification
Evidence considered
- ATM HBOP criteria table marks PM1 not applicable
Sources
PM4 N/AThis is not a stop-loss variant. The ATM HBOP framework reserves PM4 for stop-loss variants, so PM4 is not applicable. Details ▾Hide ▴
Rule
ATM PM4 applies to stop-loss variants
Evidence considered
- Variant is nonsense
- not stop-loss
Sources
PM6 VCEPThe ATM HBOP specification lists PM6 as not applicable for this gene-disease framework. Details ▾Hide ▴
VCEP rule
ATM HBOP specification
Evidence considered
- ATM HBOP criteria table marks PM6 not applicable
Sources
PP2 VCEPThe ATM HBOP specification lists PP2 as not applicable for this gene-disease framework. Details ▾Hide ▴
VCEP rule
ATM HBOP specification
Evidence considered
- ATM HBOP criteria table marks PP2 not applicable
Sources
PP3 N/AATM PP3 is specified for missense variants with REVEL greater than 0.7333 or for non-canonical splice-relevant variants with SpliceAI 0.2 or higher. This variant is a nonsense change, REVEL was not available, no SpliceAI-based splice evidence was captured, and the observed BayesDel score of 0.588046 does not create an ATM-specific PP3 pathway for a truncating variant, so PP3 is not applicable. Details ▾Hide ▴
Rule
ATM PP3 missense/splice computational rule
Evidence considered
- Nonsense consequence p.Arg805Ter
- REVEL unavailable
- SpliceAI result not captured
- BayesDel score 0.588046
Sources
PP4 VCEPThe ATM HBOP specification lists PP4 as not applicable for this gene-disease framework. Details ▾Hide ▴
VCEP rule
ATM HBOP specification
Evidence considered
- ATM HBOP criteria table marks PP4 not applicable
Sources
BS2 VCEPThe ATM HBOP specification lists BS2 as not applicable for this gene-disease framework. Details ▾Hide ▴
VCEP rule
ATM HBOP specification
Evidence considered
- ATM HBOP criteria table marks BS2 not applicable
Sources
BS4 VCEPThe ATM HBOP specification lists BS4 as not applicable for this gene-disease framework. Details ▾Hide ▴
VCEP rule
ATM HBOP specification
Evidence considered
- ATM HBOP criteria table marks BS4 not applicable
Sources
BP1 VCEPThe ATM HBOP specification lists BP1 as not applicable for this gene-disease framework. Details ▾Hide ▴
VCEP rule
ATM HBOP specification
Evidence considered
- ATM HBOP criteria table marks BP1 not applicable
Sources
BP3 VCEPThe ATM HBOP specification lists BP3 as not applicable for this gene-disease framework. Details ▾Hide ▴
VCEP rule
ATM HBOP specification
Evidence considered
- ATM HBOP criteria table marks BP3 not applicable
Sources
BP4 N/AATM BP4 is specified for missense variants with REVEL 0.249 or lower or for non-canonical splice-relevant variants with SpliceAI 0.1 or lower. This variant is a nonsense change, REVEL was not available, no SpliceAI-based splice evidence was captured, and the observed BayesDel score of 0.588046 does not create an ATM-specific BP4 pathway for a truncating variant, so BP4 is not applicable. Details ▾Hide ▴
Rule
ATM BP4 missense/splice computational rule
Evidence considered
- Nonsense consequence p.Arg805Ter
- REVEL unavailable
- SpliceAI result not captured
- BayesDel score 0.588046
Sources
BP5 VCEPThe ATM HBOP specification lists BP5 as not applicable for this gene-disease framework. Details ▾Hide ▴
VCEP rule
ATM HBOP specification
Evidence considered
- ATM HBOP criteria table marks BP5 not applicable
Sources
BP6 VCEPThe ATM HBOP specification lists BP6 as not applicable for this gene-disease framework. Details ▾Hide ▴
VCEP rule
ATM HBOP specification
Evidence considered
- ATM HBOP criteria table marks BP6 not applicable
Sources
BP7 N/AThis variant is not synonymous or deep intronic, and the ATM BP7 specification is intended for synonymous and defined intronic variants or RNA evidence showing no splice defect. BP7 is not applicable. Details ▾Hide ▴
Rule
ATM BP7 synonymous/deep-intronic framework
Evidence considered
- Variant is nonsense
- not synonymous or deep intronic
Sources
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.3
- Coding (HGVS c.)
- NM_000051.3:c.2413C>T
- Protein (HGVS p.)
- NP_000042.3:p.(Arg805Ter)
- GRCh38
- chr11:108259022 C>T
- GRCh37
- chr11:108129749 C>T
- ClinVar
- 216021
- COSMIC
- COSV53736642
Gene diagram
Every interpreted variant in ATM, mapped onto the exon structure of NM_000051.3. Select a row to find it on the plot.
ATMNM_000051.3
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
13 / 1,613,688 alleles
AF 8.06e-06 · 0 homozygotes · FAF 1.78e-05
gnomAD v2.1
10 / 251,214 alleles
AF 3.98e-05 · 0 homozygotes · FAF 0.000141
By genetic ancestry
gnomAD v4.1
AF 8.1e-06 · 13 / 1,613,688 alleles · 0 hom · FAF 1.8e-05
| East Asian3 / 44,820 | 6.7e-05 |
| South Asian3 / 91,072 | 3.3e-05 |
| Remaining individuals1 / 62,490 | 1.6e-05 |
| European (Finnish)1 / 63,850 | 1.6e-05 |
| European (non-Finnish)5 / 1,179,898 | 4.2e-06 |
0 alternate alleles recorded in 5 other groups: Admixed American, Amish, Middle Eastern, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 4e-05 · 10 / 251,214 alleles · 0 hom · FAF 0.00014
| East Asian6 / 18,388 | 0.00033 |
| South Asian2 / 30,598 | 6.5e-05 |
| European (non-Finnish)2 / 113,634 | 1.8e-05 |
0 alternate alleles recorded in 5 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 8.05608e-06; MAF= 0.00081%, 13/1613688 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 6.69344e-05; MAF= 0.00669%, 3/44820 alleles, homozygotes = 0); grpmax FAF= 1.775e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.98067e-05; MAF= 0.00398%, 10/251214 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.0003263; MAF= 0.03263%, 6/18388 alleles, homozygotes = 0); grpmax FAF= 0.00014149.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- 0.588
How the predictions were used
PP3 N/AATM PP3 is specified for missense variants with REVEL greater than 0.7333 or for non-canonical splice-relevant variants with SpliceAI 0.2 or higher. This variant is a nonsense change, REVEL was not available, no SpliceAI-based splice evidence was captured, and the observed BayesDel score of 0.588046 does not create an ATM-specific PP3 pathway for a truncating variant, so PP3 is not applicable. Details ▾Hide ▴
Rule
ATM PP3 missense/splice computational rule
Evidence considered
- Nonsense consequence p.Arg805Ter
- REVEL unavailable
- SpliceAI result not captured
- BayesDel score 0.588046
Sources
BP4 N/AATM BP4 is specified for missense variants with REVEL 0.249 or lower or for non-canonical splice-relevant variants with SpliceAI 0.1 or lower. This variant is a nonsense change, REVEL was not available, no SpliceAI-based splice evidence was captured, and the observed BayesDel score of 0.588046 does not create an ATM-specific BP4 pathway for a truncating variant, so BP4 is not applicable. Details ▾Hide ▴
Rule
ATM BP4 missense/splice computational rule
Evidence considered
- Nonsense consequence p.Arg805Ter
- REVEL unavailable
- SpliceAI result not captured
- BayesDel score 0.588046
Sources
BP7 N/AThis variant is not synonymous or deep intronic, and the ATM BP7 specification is intended for synonymous and defined intronic variants or RNA evidence showing no splice defect. BP7 is not applicable. Details ▾Hide ▴
Rule
ATM BP7 synonymous/deep-intronic framework
Evidence considered
- Variant is nonsense
- not synonymous or deep intronic
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.18). BayesDel score = 0.588046.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 27413114 ↗ATM Mutations in Cancer: Therapeutic Implications.No paper-specific finding is recorded.
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PMID 30348496 ↗Inactive Atm abrogates DSB repair in mouse cerebellum more than does Atm loss, without causing a neurological phenotype.No paper-specific finding is recorded.
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PMID 30553448 ↗Loss of ATM positively regulates Rac1 activity and cellular migration through oxidative stress.No paper-specific finding is recorded.
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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. · 2003No paper-specific finding is recorded.
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PMID 15843990 ↗ATM haplotypes and associated mutations in Iranian patients with ataxia-telangiectasia: recurring homozygosity without a founder haplotype.Babaei M et al. · 2005No paper-specific finding is recorded.
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PMID 16941484 ↗ATM mutations in Italian families with ataxia telangiectasia include two distinct large genomic deletions.Cavalieri S et al. · 2006No paper-specific finding is recorded.
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PMID 17910737 ↗Large genomic mutations within the ATM gene detected by MLPA, including a duplication of 41 kb from exon 4 to 20.Cavalieri S et al. · 2008No paper-specific finding is recorded.
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PMID 19691550 ↗Founder effects for ATM gene mutations in Italian Ataxia Telangiectasia families.Chessa L et al. · 2009No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
13 / 1,613,688 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.180
Open source ↗
ClinVar
17 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/216021/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108129749-C-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108259022-C-T?dataset=g…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.3%3Ac.2413…
- OncoKB ↗www.oncokb.org/gene/ATM/R805*
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=105143346
- 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= 8.05608e-06; MAF= 0.00081%, 13/1613688 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 6.69344e-05; MAF= 0.00669%, 3/44820 alleles, homozygotes = 0); grpmax FAF= 1.775e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.98067e-05; MAF= 0.00398%, 10/251214 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.0003263; MAF= 0.03263%, 6/18388 alleles, homozygotes = 0); grpmax FAF= 0.00014149.
ClinVar
This variant has been reported in ClinVar as Pathogenic (17 clinical laboratories) and as Pathogenic by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 216021)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.18). BayesDel score = 0.588046.
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; COSV53736642, n = 11 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.