About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.1355del, p.(Thr452AsnfsTer21)
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 is a frameshift deletion (c.1355del) in exon 10 of 63, creating a premature termination codon at p.Thr452AsnfsTer21 with predicted nonsense-mediated decay. Loss of function is an established disease mechanism for ATM (ataxia-telangiectasia, autosomal recessive; cancer susceptibility, autosomal dominant). Under the ATM VCEP v1.5.0 PVS1 Decision Tree, this NMD-prone frameshift variant upstream of p.Arg3047 qualifies for PVS1_VeryStrong.
PM5Supporting
PM5 · supporting
This frameshift deletion creates a premature termination codon at p.Thr452AsnfsTer21 (codon 472), which is upstream of p.Arg3047, the most C-terminal known pathogenic variant in ATM. Under ATM VCEP v1.5.0, PM5_Supporting is applied to frameshifting or truncating variants with PTCs upstream of p.Arg3047.
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
27 / 1,614,094 alleles
gnomAD v4.1: 27 / 1,614,094 alleles. Recorded AF 1.67277e-05. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
No listed criterion applied
SpliceAI score
0.020 maximum delta
Recorded SpliceAI maximum delta score: 0.020. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
9 reported laboratory submissions
7 Pathogenic · 1 pathogenic · 1 Likely 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
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV99069690, n = 1 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 · 5 not met · 5 not assessed · 15 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.1355del (NP_000042.3:p.Thr452AsnfsTer21) is a frameshift deletion in exon 10 of the ATM gene, creating a premature termination codon at position 472 with predicted nonsense-mediated decay.
PVS1_VeryStrong is applied: the variant is a predicted null allele in a gene where loss of function is an established disease mechanism for ataxia-telangiectasia (autosomal recessive) and cancer susceptibility (autosomal dominant). The PTC is well upstream of p.Arg3047 and the affected exon is constitutive per the ATM VCEP v1.5.0.
PM5_Supporting is applied: the premature termination codon at codon 472 lies upstream of p.Arg3047, the most C-terminal known pathogenic variant in ATM, meeting the VCEP truncation-cutoff rule for PM5_Supporting.
This variant has been reported in ClinVar as Pathogenic by the ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer VCEP (expert panel, reviewed status) and by nine clinical laboratories (8 Pathogenic, 1 Likely pathogenic; ClinVar VariationID 141474).
The variant is extremely rare in population databases: gnomAD v4.1 allele frequency = 0.00167% (27/1,614,094 alleles, 0 homozygotes) and absent from gnomAD v2.1 and gnomAD-Canada v1.0. The grpmax filtering AF of 0.0015% is well below the BA1 (>0.5%) and BS1 (>0.05%) thresholds, confirming the variant is not a common benign polymorphism.
SpliceAI predicts no cryptic splice impact (max delta = 0.02), consistent with the variant exerting its pathogenic effect through protein truncation rather than aberrant splicing.
The variant has been observed in somatic cancers (COSMIC COSV99069690, n=1), consistent with its role as a loss-of-function allele in ATM-related tumorigenesis.
Under the ATM VCEP v1.5.0 combination rules (Richards et al. 2015), the criteria met are PVS1_VeryStrong and PM5_Supporting (1 Pathogenic Very Strong + 1 Pathogenic Supporting). No formal combination rule in the VCEP framework maps exactly to this criterion set; the closest rule (Rule 10: 1 PVS + 1 PM) reaches Likely Pathogenic but requires a Pathogenic Moderate criterion which is not met. However, the ClinGen HBOP VCEP has independently classified this variant as Pathogenic based on their full evidentiary review including proband-level PM3/BP2 data not available in this assessment.
Limitations of this assessment: (a) all five full-text publications retrieved were non-viable (Sci-Hub landing pages without paper content), preventing verification of variant-specific proband counts, segregation data, or functional assay results; (b) PM3 proband-level data referenced by the VCEP expert panel was not available for independent adjudication; (c) PS3/BS3 functional assay results could not be verified.
No criteria match.
Met · 3
PVS1 Very strongThis is a frameshift deletion (c.1355del) in exon 10 of 63, creating a premature termination codon at p.Thr452AsnfsTer21 with predicted nonsense-mediated decay. Loss of function is an established disease mechanism for ATM (ataxia-telangiectasia, autosomal recessive; cancer susceptibility, autosomal dominant). Under the ATM VCEP v1.5.0 PVS1 Decision Tree, this NMD-prone frameshift variant upstream of p.Arg3047 qualifies for PVS1_VeryStrong. Details ▾Hide ▴
Evidence considered
- Frameshift deletion in exon 10/63
- PTC at codon 472
- NMD-predicted
- LOF is established disease mechanism per ClinGen HBOP VCEP v1.5.0
- PTC is upstream of p.Arg3047
- the most C-terminal known pathogenic variant
Still missing
- No RNA studies confirming NMD for this specific allele
- but frameshift prediction is sufficient per VCEP guidance
Sources
PM5 SupportingThis frameshift deletion creates a premature termination codon at p.Thr452AsnfsTer21 (codon 472), which is upstream of p.Arg3047, the most C-terminal known pathogenic variant in ATM. Under ATM VCEP v1.5.0, PM5_Supporting is applied to frameshifting or truncating variants with PTCs upstream of p.Arg3047. Details ▾Hide ▴
Evidence considered
- PTC at codon 472 is upstream of p.Arg3047 boundary
- VCEP specifies PM5_Supporting (not moderate) for truncating variants upstream of this cutoff
Sources
Not met · 5 · evaluated, threshold not reached
PM2 The gnomAD v4.1 allele frequency is 0.00167% (27/1,614,094 alleles; grpmax FAF=1.53e-05), which exceeds the ATM VCEP threshold of <=0.001%. While the variant is absent from gnomAD v2.1 and extremely rare overall, the VCEP specifies the v4 dataset exclusively for PM2_Supporting and the observed frequency is above the cutoff. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: AF=0.00167% (27/1
- 614
- 094)
- grpmax FAF=1.533e-05
- nfe sub-pop AF=0.00220% (26/1
- 180
- 034)
- gnomAD v2.1: absent
- gnomAD-Canada v1.0: absent
- VCEP cutoff: frequency <=0.001% in gnomAD v4
Sources
PP3 This is a frameshift deletion, not a missense variant, so the REVEL threshold (>0.7333) does not apply. SpliceAI predicts no significant splice impact (max delta score = 0.02, below the 0.2 threshold for splicing PP3). Additionally, the ATM VCEP notes that PP3 for splice predictions may not be applied in addition to PVS1 or PVS1_Variable(RNA) codes. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02 (threshold for splicing PP3 is >=0.2)
- Variant is a frameshift deletion
- not missense
- REVEL score not available for non-missense variants
Sources
BA1 The gnomAD v4.1 grpmax filtering allele frequency is 1.533e-05 (0.0015%), far below the ATM VCEP BA1 threshold of >0.5%. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 1.533e-05 (0.0015%)
- VCEP BA1 threshold: grpmax FAF >0.5%
Sources
BS1 The gnomAD v4.1 grpmax filtering allele frequency is 1.533e-05 (0.0015%), below the ATM VCEP BS1 threshold of >0.05%. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 1.533e-05 (0.0015%)
- VCEP BS1 threshold: grpmax FAF >0.05%
Sources
BP4 While SpliceAI shows no predicted splice impact (max delta = 0.02, below the VCEP BP4 threshold of <=0.1), BP4 is intended to provide benign computational evidence. For a frameshift deletion where the pathogenic mechanism is protein truncation via NMD, the absence of a cryptic splice effect does not constitute benign evidence — the variant is damaging through its primary coding effect. BP4 does not apply. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02 (<=0.1)
- Variant mechanism is frameshift/protein truncation
- not splicing
- Absence of splice defect does not mitigate the frameshift's damaging effect
Sources
Not assessed · 5 · no assessment recorded
PS3 No variant-specific functional assay data identified for NM_000051.4:c.1355del. OncoKB curates the variant as Likely Loss-of-function, but this is a curated literature gateway and not a direct functional evidence source. All five full-text papers retrieved were non-viable (Sci-Hub landing pages without paper content). Without access to primary functional data, PS3 cannot be assessed. Details ▾Hide ▴
Evidence considered
- OncoKB annotation: Likely Oncogenic
- Likely Loss-of-function (gateway curation
- not primary evidence)
- No primary functional assay results available for this exact variant
Still missing
- No variant-specific functional studies (e.g.
- ATM kinase activity
- radiosensitivity rescue) identified
- Full-text papers unavailable for verification
Sources
PS4 ATM VCEP v1.5.0 requires formal case-control studies (p<=0.05 AND either OR/HR/RR >=2 or lower 95% CI >=1.5). PS4_Moderate is explicitly not for use. Nine clinical laboratories have submitted this variant as P/LP in ClinVar, suggesting multiple independent proband observations, but no formal case-control study or calibrated proband count has been identified for this variant. Details ▾Hide ▴
Evidence considered
- ClinVar: Pathogenic (7 labs)
- pathogenic (1 lab)
- Likely pathogenic (1 lab)
- ClinVar expert panel classification: Pathogenic (ClinGen HBOP VCEP)
- gnomAD v4.1: extremely rare (27/1
- 614
- 094 alleles)
- absent from v2.1
- No published case-control study with OR/RR for this variant
Still missing
- No case-control study with odds ratio or relative risk for this variant
- Proband counting not calibrated per VCEP population-specific requirements
Sources
PP1 No segregation data available for this variant. ATM VCEP v1.5.0 limits PP1 to AR condition with both variants identified in proband and affected relatives having both variants. PP1 is not used for the AD condition (low penetrance). All full-text papers were non-viable (Sci-Hub landing pages); no pedigree or co-segregation information could be verified. Details ▾Hide ▴
Evidence considered
- No segregation or pedigree data identified in available sources
Still missing
- No co-segregation data with disease in multiple affected family members
- Full-text papers unavailable for variant-specific pedigree extraction
BS3 No variant-specific benign functional data identified for NM_000051.4:c.1355del. BS3 requires well-established in vitro or in vivo functional studies showing no damaging effect (e.g., rescue of ATM-specific phosphorylation AND radiosensitivity). All available evidence points toward loss of function. Full-text papers were non-viable for verification. Details ▾Hide ▴
Evidence considered
- No functional studies demonstrating normal ATM activity for this variant
- OncoKB annotation: Likely Loss-of-function (contrary to BS3 requirements)
Still missing
- No assays showing this variant retains normal ATM function
- All functional context suggests loss of function
- not benign effect
BP2 BP2 requires observation of this variant in trans with a pathogenic ATM variant in an unaffected individual (aged 18+ with no evidence of A-T). No such data has been identified. The ATM PM3/BP2 table requires proband-level information not available in the current evidence set. Details ▾Hide ▴
Evidence considered
- No data on unaffected individuals carrying this variant in trans with a P/LP ATM variant
Still missing
- No proband-level data available
- No unaffected individuals with biallelic ATM variants reported
Not applicable · 15· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 under ATM VCEP v1.5.0 applies to missense changes with the same amino acid substitution as a known pathogenic variant, or to splicing variants using the PS1 Splicing table. This is a frameshift deletion and does not fit either category. Details ▾Hide ▴
Evidence considered
- Variant is a frameshift deletion
- not a missense or splicing variant
Sources
PS2 VCEPATM VCEP v1.5.0 explicitly states PS2 is not applicable: informative de novo occurrences have not been observed and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
PM1 VCEPATM VCEP v1.5.0 explicitly states PM1 is not applicable: benign and pathogenic variants are known to occur within the same domains and germline mutational hotspots are not well defined at this time. Details ▾Hide ▴
PM4 N/AATM VCEP v1.5.0 restricts PM4 to stop-loss variants only. This is a frameshift deletion, not a stop-loss variant. In-frame deletions/insertions less than a single exon are also excluded. Details ▾Hide ▴
PM6 VCEPATM VCEP v1.5.0 explicitly states PM6 is not applicable: de novo occurrences have not been observed and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
PP2 VCEPATM VCEP v1.5.0 explicitly states PP2 is not applicable: ATM does not have a defined low rate of missense benign variation. Details ▾Hide ▴
PP4 VCEPATM VCEP v1.5.0 states PP4 is not applicable: for autosomal dominant, breast cancer has multiple genetic etiologies; for autosomal recessive, such evidence is built into the PM3/BP2 table. Details ▾Hide ▴
BS2 VCEPATM VCEP v1.5.0 explicitly states BS2 is not applicable: ATM has incomplete penetrance. Details ▾Hide ▴
BS4 VCEPATM VCEP v1.5.0 states BS4 is not applicable: for AD, co-segregation analysis in low-penetrance genes can lead to false positives; for AR, informative instances of lack of co-segregation in A-T families are too rare. Details ▾Hide ▴
BP1 VCEPATM VCEP v1.5.0 explicitly states BP1 is not applicable: missense pathogenic variants are known for ATM. Details ▾Hide ▴
BP3 VCEPATM VCEP v1.5.0 explicitly states BP3 is not applicable. Additionally, this is a frameshift deletion, not an in-frame deletion in a repetitive region without known function. Details ▾Hide ▴
Evidence considered
- VCEP specification: do not use
- Variant is a frameshift deletion
- not an in-frame deletion in a repetitive region
Sources
BP5 VCEPATM VCEP v1.5.0 explicitly states BP5 is not applicable: cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype, and ATM has low penetrance with natural co-occurrence of other pathogenic variants. Details ▾Hide ▴
BP6 VCEPATM VCEP v1.5.0 explicitly states BP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP7 N/AATM VCEP v1.5.0 restricts BP7 to synonymous and deep intronic variants. This is a coding frameshift deletion and does not qualify. Details ▾Hide ▴
PS5 N/APS5 is not a standard ACMG/AMP criterion and is not defined in the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.1355del
- Protein (HGVS p.)
- NP_000042.3:p.(Thr452AsnfsTer21)
- GRCh38
- chr11:108250819 AC>A
- GRCh37
- chr11:108121546 AC>A
- ClinVar
- 141474
- COSMIC
- COSV99069690
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
27 / 1,614,094 alleles
AF 1.67e-05 · 0 homozygotes · FAF 1.53e-05
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 1.7e-05 · 27 / 1,614,094 alleles · 0 hom · FAF 1.5e-05
| European (non-Finnish)26 / 1,180,034 | 2.2e-05 |
| Remaining individuals1 / 62,508 | 1.6e-05 |
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.67277e-05; MAF= 0.00167%, 27/1614094 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.20333e-05; MAF= 0.00220%, 26/1180034 alleles, homozygotes = 0); grpmax FAF= 1.533e-05.
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 This is a frameshift deletion, not a missense variant, so the REVEL threshold (>0.7333) does not apply. SpliceAI predicts no significant splice impact (max delta score = 0.02, below the 0.2 threshold for splicing PP3). Additionally, the ATM VCEP notes that PP3 for splice predictions may not be applied in addition to PVS1 or PVS1_Variable(RNA) codes. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02 (threshold for splicing PP3 is >=0.2)
- Variant is a frameshift deletion
- not missense
- REVEL score not available for non-missense variants
Sources
BP4 While SpliceAI shows no predicted splice impact (max delta = 0.02, below the VCEP BP4 threshold of <=0.1), BP4 is intended to provide benign computational evidence. For a frameshift deletion where the pathogenic mechanism is protein truncation via NMD, the absence of a cryptic splice effect does not constitute benign evidence — the variant is damaging through its primary coding effect. BP4 does not apply. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02 (<=0.1)
- Variant mechanism is frameshift/protein truncation
- not splicing
- Absence of splice defect does not mitigate the frameshift's damaging effect
Sources
BP7 N/AATM VCEP v1.5.0 restricts BP7 to synonymous and deep intronic variants. This is a coding frameshift deletion and does not qualify. Details ▾Hide ▴
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
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
-
PMID 27413114 ↗ATM Mutations in Cancer: Therapeutic Implications.No paper-specific finding is recorded.
-
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.
-
PMID 30553448 ↗Loss of ATM positively regulates Rac1 activity and cellular migration through oxidative stress.No paper-specific finding is recorded.
-
PMID 10234507 ↗Rapid and efficient ATM mutation detection by fluorescent chemical cleavage of mismatch: identification of four novel mutations.Izatt L et al. · 1999No paper-specific finding is recorded.
-
PMID 11821961 ↗Breakpoints in the ataxia telangiectasia gene arise at the RGYW somatic hypermutation motif.Bradshaw PS et al. · 2002No paper-specific finding is recorded.
-
PMID 15928302 ↗Cancer risks and mortality in heterozygous ATM mutation carriers.Thompson D et al. · 2005No paper-specific finding is recorded.
-
PMID 22585167 ↗ATM mutations in patients with hereditary pancreatic cancer.Roberts NJ et al. · 2012No paper-specific finding is recorded.
-
PMID 23807571 ↗Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients.Huang Y et al. · 2013No 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
27 / 1,614,094 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.020
Open source ↗
ClinVar
7 Pathogenic · 1 pathogenic · 1 Likely 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/141474/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108121546-AC-A?dataset=gno…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108250819-AC-A?dataset=…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.1355…
- OncoKB ↗www.oncokb.org/gene/ATM/T452Nfs*21
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=122714700
- 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= 1.67277e-05; MAF= 0.00167%, 27/1614094 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.20333e-05; MAF= 0.00220%, 26/1180034 alleles, homozygotes = 0); grpmax FAF= 1.533e-05.
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
This variant has been reported in ClinVar as Pathogenic (7 clinical laboratories) and as pathogenic (1 clinical laboratory) and as Likely pathogenic (1 clinical laboratory) and as Pathogenic by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 141474)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
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; COSV99069690, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.