About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.8751C>T, p.(Gly2917=)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign 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: 1
Benign evidence criteria: 3
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
PM2_Supporting is met under ATM VCEP v1.5.0. The variant frequency in gnomAD v4.1 is 0.00019% (3/1,613,812 alleles; grpmax FAF = 6.8e-07), which is ≤ 0.001%, meeting the VCEP PM2_Supporting threshold. The variant is absent from gnomAD v2.1, consistent with extreme rarity.
Benign criteria applied · 3
BP4Supporting
BP4 · supporting
BP4_Supporting is met under ATM VCEP v1.5.0 (splicing path). The variant has no predicted impact on splicing: SpliceAI max delta score = 0.01, which is ≤ 0.1, meeting the VCEP BP4 threshold for benign computational splicing prediction. No REVEL score is available as this is a synonymous variant (the missense path is not applicable).
BP6Supporting
BP6 · supporting
Expert panel ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen classified as Likely benign.
BP7Supporting
BP7 · supporting
BP7_Supporting is met under ATM VCEP v1.5.0. This is a synonymous variant (c.8751C>T, p.Gly2917=) located at nucleotide position c.8751 within exon 62 (c.8654 to c.8803). The variant lies 52 nucleotides upstream of the donor site and 97 nucleotides downstream of the acceptor site, well beyond the VCEP-defined boundaries of +7 (donor) and -21 (acceptor). SpliceAI predicts no splice impact (max delta = 0.01). No aberrant RNA defect has been observed or predicted for this variant.
Recorded classification: Likely benign
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework: matched Rule19 (Benign.Supporting >=2) with applied criteria: PM2 supporting, BP4 supporting, BP6 supporting benign, BP7 supporting; maps to Likely Benign.
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
3 / 1,613,812 alleles
gnomAD v4.1: 3 / 1,613,812 alleles. Recorded AF 1.85895e-06. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
4 reported laboratory submissions
2 Likely benign · 1 Benign · 1 Uncertain significance.
Functional evidence
Statement recorded
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV113466872, 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.
26 criteria with recorded statuses: 4 met · 4 not met · 5 not assessed · 13 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
This synonymous variant (NM_000051.3:c.8751C>T, p.Gly2917=) is located in exon 62 of ATM, well removed from canonical splice sites (52 nt from the donor, 97 nt from the acceptor). SpliceAI predicts no splice impact (max delta = 0.01), consistent with BP4_Supporting under the ATM HBOP VCEP v1.5.0.
As a synonymous variant not near splice consensus boundaries and with no predicted or observed splice defect, BP7_Supporting is met under ATM VCEP v1.5.0.
The variant is extremely rare in population databases: absent from gnomAD v2.1 and present at AF = 0.00019% (3/1,613,812 alleles, grpmax FAF = 6.8e-07) in gnomAD v4.1, meeting PM2_Supporting under ATM VCEP v1.5.0 (threshold ≤ 0.001%).
This variant has been classified as Likely Benign by the ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer VCEP (ClinVar Variation ID 453745, reviewed by expert panel). Clinical laboratory submissions include Likely Benign (2 labs), Benign (1 lab), and Uncertain Significance (1 lab).
PVS1, PS1, and PM5 are not applicable as the variant is synonymous and does not cause a null effect, amino acid change, or premature termination codon. PS3 and BS3 functional assay data (ATM kinase/rescue assays) are not available. PS4 case-control data and PP1 segregation data are absent. BA1 and BS1 population frequency thresholds are not met. PP3 computational evidence for pathogenicity is not met.
Under the ATM VCEP v1.5.0 combination rules (adapted from Richards et al. 2015), the met criteria include two benign supporting criteria (BP4, BP7) and one pathogenic supporting criterion (PM2). Per the VCEP classification framework, this constellation of ≥1 Benign Supporting and ≥1 Pathogenic Supporting results in Uncertain Significance - Conflicting Evidence (Rule 31). However, the ClinGen HBOP VCEP expert panel has classified this variant as Likely Benign, suggesting additional benign evidence (such as RNA splicing data from PMID 34974520) may have been considered in the expert panel curation that is not independently verifiable from the available case materials.
No criteria match.
Met · 4
PM2 SupportingPM2_Supporting is met under ATM VCEP v1.5.0. The variant frequency in gnomAD v4.1 is 0.00019% (3/1,613,812 alleles; grpmax FAF = 6.8e-07), which is ≤ 0.001%, meeting the VCEP PM2_Supporting threshold. The variant is absent from gnomAD v2.1, consistent with extreme rarity. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: AF = 0.00019% (3/1
- 613
- 812 alleles)
- grpmax FAF = 6.8e-07
- gnomAD v2.1: absent
Sources
BP4 SupportingBP4_Supporting is met under ATM VCEP v1.5.0 (splicing path). The variant has no predicted impact on splicing: SpliceAI max delta score = 0.01, which is ≤ 0.1, meeting the VCEP BP4 threshold for benign computational splicing prediction. No REVEL score is available as this is a synonymous variant (the missense path is not applicable). Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score = 0.01 (≤ 0.1 threshold for BP4_Supporting)
Sources
BP6 SupportingExpert panel ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen classified as Likely benign. Details ▾Hide ▴
BP7 SupportingBP7_Supporting is met under ATM VCEP v1.5.0. This is a synonymous variant (c.8751C>T, p.Gly2917=) located at nucleotide position c.8751 within exon 62 (c.8654 to c.8803). The variant lies 52 nucleotides upstream of the donor site and 97 nucleotides downstream of the acceptor site, well beyond the VCEP-defined boundaries of +7 (donor) and -21 (acceptor). SpliceAI predicts no splice impact (max delta = 0.01). No aberrant RNA defect has been observed or predicted for this variant. Details ▾Hide ▴
Evidence considered
- Synonymous variant at c.8751 (exon 62)
- 52 nt from donor
- 97 nt from acceptor
- SpliceAI max delta = 0.01
Sources
Not met · 4 · evaluated, threshold not reached
PP3 PP3 is not met. The ATM VCEP v1.5.0 requires REVEL > 0.733 for missense variants or SpliceAI ≥ 0.2 for splicing variants. This is a synonymous variant; REVEL is not available (no amino acid substitution to score). SpliceAI max delta score is 0.01, well below the 0.2 threshold. No computational evidence supports a damaging effect. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (< 0.2 threshold)
- REVEL not available for synonymous variant
Sources
BA1 BA1 is not met. The ATM VCEP v1.5.0 requires grpmax Filtering AF > 0.5% in gnomAD v4. The observed grpmax FAF for c.8751C>T is 6.8e-07 (0.000068%), which is orders of magnitude below the 0.5% threshold. This variant is extremely rare, not a common polymorphism. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 6.8e-07 (0.000068%)
- threshold is 0.5%
Sources
BS1 BS1 is not met. The ATM VCEP v1.5.0 requires grpmax Filtering AF > 0.05% in gnomAD v4. The observed grpmax FAF for c.8751C>T is 6.8e-07 (0.000068%), well below the 0.05% threshold. The population frequency does not support a benign interpretation. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 6.8e-07 (0.000068%)
- threshold is 0.05%
Sources
PS5 PS5 is not met. Under generic ACMG/AMP 2015 (the ATM VCEP does not include PS5), this criterion requires a reputable source to have reported the variant as pathogenic. ClinVar submissions for this variant (Variation ID 453745) are Likely Benign (expert panel and 2 clinical laboratories), Benign (1 clinical laboratory), and Uncertain Significance (1 clinical laboratory). No reputable source has reported c.8751C>T as pathogenic. Details ▾Hide ▴
Evidence considered
- ClinVar: Likely Benign (expert panel)
- Likely Benign (2 labs)
- Benign (1 lab)
- VUS (1 lab)
- no pathogenic assertion
Sources
Not assessed · 5 · no assessment recorded
PS3 PS3 is not assessed. The ATM VCEP v1.5.0 requires functional evidence demonstrating that the variant fails to rescue ATM-specific features (e.g., phosphorylation of ATM-specific targets) and/or radiosensitivity. No validated functional assay data meeting VCEP PS3 specifications was identified for this variant. An exploratory search identified a minigene splicing assay (Lhota et al. 2021, PMID 34974520) reportedly showing normal splicing, but (a) this could not be independently verified as full text was unavailable, and (b) normal splicing evidence does not directly fulfill VCEP PS3 criteria, which require rescue-based functional assays. Details ▾Hide ▴
Still missing
- No functional assay (kinase activity
- radiosensitivity rescue) data available for c.8751C>T
- PMID 34974520 (Lhota et al. 2021) reportedly shows normal splicing but full text unavailable for verification
- this would support BP7(RNA) rather than PS3
PS4 PS4 is not assessed. The ATM VCEP v1.5.0 requires a case-control study with p ≤ 0.05 and OR/HR/RR ≥ 2 (or lower 95% CI ≥ 1.5). No published case-control study analyzing the prevalence of c.8751C>T in affected versus control populations was identified. The variant is present at very low frequency in gnomAD v4.1 (AF = 0.00019%) and absent from gnomAD v2.1, precluding population-based enrichment analysis without dedicated case-control data. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: absent
- gnomAD v4.1: 3/1
- 613
- 812 alleles (AF = 0.00019%)
Still missing
- No case-control study with variant-specific odds ratio for c.8751C>T
- No systematic cohort enrichment data in breast/ovarian/pancreatic cancer or A-T patient cohorts
Sources
PP1 PP1 is not assessed. The ATM VCEP v1.5.0 applies PP1 for autosomal recessive (A-T) conditions with segregation in affected relatives (≥1 supporting, 2 moderate, ≥3 strong). No segregation data for c.8751C>T in A-T or cancer-affected families was identified in any of the available sources. Details ▾Hide ▴
Still missing
- No segregation data available for c.8751C>T in any family
- No co-segregation studies in A-T or hereditary cancer pedigrees
BS3 BS3 is not assessed. The ATM VCEP v1.5.0 requires functional evidence that the variant rescues ATM-specific features (e.g., phosphorylation of ATM-specific targets) and/or radiosensitivity (Moderate: both; Supporting: either). No validated functional rescue assay data was identified. An exploratory search identified a minigene splicing assay (Lhota et al. 2021, PMID 34974520) reportedly demonstrating normal splicing for c.8751C>T; however, (a) full text was unavailable for independent verification, and (b) normal splicing evidence is more appropriately considered under BP7(RNA) rather than BS3 under the VCEP framework. Details ▾Hide ▴
Still missing
- No functional rescue assay (kinase activity
- radiosensitivity) available for c.8751C>T
- PMID 34974520 minigene data reportedly shows normal splicing
- full text verification needed for BP7(RNA) consideration
BP2 BP2 is not assessed. Under the ATM VCEP v1.5.0 PM3/BP2 table, BP2 applies when the variant is observed in trans with a P/LP variant in an unaffected (non-A-T) individual, with points assigned per proband. No data on co-occurrence in trans with a known pathogenic ATM variant in unaffected individuals was identified for c.8751C>T. Details ▾Hide ▴
Still missing
- No phasing data or co-occurrence observations for c.8751C>T with known pathogenic ATM variants in unaffected individuals
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable. This is a synonymous variant (c.8751C>T, p.Gly2917=) with no predicted splice impact (SpliceAI max delta score = 0.01) and no evidence of aberrant splicing. It does not meet the ATM VCEP v1.5.0 PVS1 null-variant criteria (nonsense, frameshift, canonical ±1,2 splice sites, initiation codon, or exon deletion) and does not trigger PVS1_Variable(RNA) as no splice defect is observed or predicted. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score = 0.01
- synonymous variant with no amino acid change
Sources
PS1 N/APS1 is not applicable. The ATM VCEP v1.5.0 PS1 rule applies to missense changes (requiring same amino acid change as a known P/LP variant) or splicing variants with similar splice predictions. This is a synonymous variant (p.Gly2917=) with no amino acid change, and SpliceAI (max delta = 0.01) predicts no splice impact. Neither branch of the VCEP PS1 rule is triggered. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- no amino acid change
- SpliceAI max delta = 0.01
Sources
PS2 VCEPPS2 is not applicable. The ATM HBOP VCEP v1.5.0 explicitly marks PS2 as Not Applicable. Details ▾Hide ▴
PM1 VCEPPM1 is not applicable. The ATM HBOP VCEP v1.5.0 explicitly marks PM1 as Not Applicable. Details ▾Hide ▴
PM5 N/APM5 is not applicable. The ATM VCEP v1.5.0 PM5 rule applies to frameshifting/truncating variants with premature termination codons upstream of p.Arg3047, or to splice variants with observed splice defects where PVS1_VS(RNA) is applied. This variant (c.8751C>T) is a synonymous substitution that does not create a premature termination codon and has no predicted or observed splice impact (SpliceAI max delta = 0.01). The pm5_candidates.json confirms no comparator truncating/splice variants are applicable. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- no PTC created
- SpliceAI max delta = 0.01
- no PM5-eligible comparators identified
Sources
PM6 VCEPPM6 is not applicable. The ATM HBOP VCEP v1.5.0 explicitly marks PM6 as Not Applicable. Details ▾Hide ▴
PP2 VCEPPP2 is not applicable. The ATM HBOP VCEP v1.5.0 explicitly marks PP2 as Not Applicable. Details ▾Hide ▴
PP4 VCEPPP4 is not applicable. The ATM HBOP VCEP v1.5.0 explicitly marks PP4 as Not Applicable. Details ▾Hide ▴
PP5 VCEPPP5 is not applicable. The ATM HBOP VCEP v1.5.0 explicitly marks PP5 as Not Applicable. Details ▾Hide ▴
BS2 VCEPBS2 is not applicable. The ATM HBOP VCEP v1.5.0 explicitly marks BS2 as Not Applicable. Details ▾Hide ▴
BS4 VCEPBS4 is not applicable. The ATM HBOP VCEP v1.5.0 explicitly marks BS4 as Not Applicable. Details ▾Hide ▴
BP1 VCEPBP1 is not applicable. The ATM HBOP VCEP v1.5.0 explicitly marks BP1 as Not Applicable. Details ▾Hide ▴
BP5 VCEPBP5 is not applicable. The ATM HBOP VCEP v1.5.0 explicitly marks BP5 as Not Applicable. Details ▾Hide ▴
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.3
- Coding (HGVS c.)
- NM_000051.3:c.8751C>T
- Protein (HGVS p.)
- NP_000042.3:p.(Gly2917=)
- GRCh38
- chr11:108353845 C>T
- GRCh37
- chr11:108224572 C>T
- ClinVar
- 453745
- COSMIC
- COSV113466872
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
3 / 1,613,812 alleles
AF 1.86e-06 · 0 homozygotes · FAF 6.8e-07
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 1.9e-06 · 3 / 1,613,812 alleles · 0 hom · FAF 6.8e-07
| European (non-Finnish)3 / 1,179,944 | 2.5e-06 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, 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= 1.85895e-06; MAF= 0.00019%, 3/1613812 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.54249e-06; MAF= 0.00025%, 3/1179944 alleles, homozygotes = 0); grpmax FAF= 6.8e-07.
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingBP4_Supporting is met under ATM VCEP v1.5.0 (splicing path). The variant has no predicted impact on splicing: SpliceAI max delta score = 0.01, which is ≤ 0.1, meeting the VCEP BP4 threshold for benign computational splicing prediction. No REVEL score is available as this is a synonymous variant (the missense path is not applicable). Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score = 0.01 (≤ 0.1 threshold for BP4_Supporting)
Sources
BP7 SupportingBP7_Supporting is met under ATM VCEP v1.5.0. This is a synonymous variant (c.8751C>T, p.Gly2917=) located at nucleotide position c.8751 within exon 62 (c.8654 to c.8803). The variant lies 52 nucleotides upstream of the donor site and 97 nucleotides downstream of the acceptor site, well beyond the VCEP-defined boundaries of +7 (donor) and -21 (acceptor). SpliceAI predicts no splice impact (max delta = 0.01). No aberrant RNA defect has been observed or predicted for this variant. Details ▾Hide ▴
Evidence considered
- Synonymous variant at c.8751 (exon 62)
- 52 nt from donor
- 97 nt from acceptor
- SpliceAI max delta = 0.01
Sources
PP3 PP3 is not met. The ATM VCEP v1.5.0 requires REVEL > 0.733 for missense variants or SpliceAI ≥ 0.2 for splicing variants. This is a synonymous variant; REVEL is not available (no amino acid substitution to score). SpliceAI max delta score is 0.01, well below the 0.2 threshold. No computational evidence supports a damaging effect. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (< 0.2 threshold)
- REVEL not available for synonymous variant
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
10 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 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.No paper-specific finding is recorded.
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PMID 34242744 ↗Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.No paper-specific finding is recorded.
-
PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004No paper-specific finding is recorded.
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PMID 17508274 ↗Risk assessment and genetic counseling for hereditary breast and ovarian cancer: recommendations of the National Society of Genetic Counselors.Berliner JL et al. · 2007No paper-specific finding is recorded.
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PMID 18163131 ↗The emerging landscape of breast cancer susceptibility.Stratton MR et al. · 2008No paper-specific finding is recorded.
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PMID 20301317 ↗Hereditary Ataxia Overview.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 20301425 ↗BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 20301790 ↗Ataxia-Telangiectasia.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 20050888 ↗EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias.Gasser T et al. · 2010No 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
3 / 1,613,812 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
2 Likely benign · 1 Benign · 1 Uncertain significance
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/453745/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108224572-C-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108353845-C-T?dataset=g…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.3%3Ac.8751…
- OncoKB ↗www.oncokb.org/gene/ATM/G2917=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=122743437
- 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= 1.85895e-06; MAF= 0.00019%, 3/1613812 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.54249e-06; MAF= 0.00025%, 3/1179944 alleles, homozygotes = 0); grpmax FAF= 6.8e-07.
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
This variant has been reported in ClinVar as Likely benign (2 clinical laboratories) and as Benign (1 clinical laboratory) and as Uncertain significance (1 clinical laboratory) and as Likely Benign by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 453745)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
Functional
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV113466872, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.