About CHEK2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
CHEK2 c.1513T>A, p.(Ser505Thr)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen CHEK2 VCEP v1.0.0. 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: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
NM_007194.4:c.1513T>A is present at very low frequency in general population databases. gnomAD v2.1: 17/233,642 alleles (AF=0.00728%). gnomAD v4.1: 44/1,595,378 alleles (AF=0.00276%). The highest subpopulation frequency is in East Asians at 0.083% (v2.1, 15/17,996) and 0.078% (v4.1, 35/44,872), both below the 0.1% PM2 threshold for a gene with CHEK2-associated cancer predisposition. No homozygotes observed. Absent from gnomAD-Canada.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence unanimously predict no damaging effect for p.Ser505Thr. REVEL score is 0.018 (benign range), BayesDel score is -0.428 (benign range), and SpliceAI predicts no splice alteration (max delta = 0.00). These complementary in silico tools provide consistent evidence that the missense substitution is tolerated at the protein level.
Recorded classification: Uncertain significance
Hereditary Breast, Ovarian and Pancreatic Cancer Specification v1.0.0 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting; combination = 1 supporting + 1 supporting benign, which maps to VUS.
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
44 / 1,595,378 alleles
gnomAD v4.1: 44 / 1,595,378 alleles. Recorded AF 2.75797e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.27609e-05; MAF= 0.00728%, 17/233642 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000833519; MAF= 0.08335%, 15/17996 alleles, homozygotes = 0); grpmax FAF= 0.00051369.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
6 reported laboratory submissions
4 Likely benign · 1 Uncertain significance · 1 likely benign.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. CHEK2, an intracellular kinase involved in control of the cell cycle, is altered in various cancer types.
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 CHEK2 VCEP v1.0.0, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 15 not met · 3 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_007194.4:c.1513T>A (p.Ser505Thr) is a missense variant in exon 14 of CHEK2, a gene associated with autosomal dominant hereditary breast, ovarian, pancreatic, and prostate cancer predisposition.
This variant is present at very low frequency in gnomAD: 17/233,642 alleles in v2.1 (AF=0.00728%) and 44/1,595,378 alleles in v4.1 (AF=0.00276%), with the highest subpopulation frequency of 0.083% in East Asians, all below the 0.1% PM2 threshold (PM2_Supporting).
Multiple in silico tools unanimously predict a benign effect: REVEL score 0.018 (benign range), BayesDel score -0.428 (benign range), and SpliceAI max delta 0.00 (no predicted splice impact) (BP4_Supporting).
PVS1 is not applicable as this is a missense variant, not a null variant. PS1 and PM5 are not applicable as no same-residue pathogenic comparators have been identified. BP7 is not applicable as the variant is not synonymous.
ClinVar consensus is Likely benign from four clinical laboratories, with one additional submitter reporting Uncertain significance and one reporting likely benign. No expert panel classification is available, and no reputable source has classified this variant as pathogenic.
Functional evidence (PS3/BS3) remains unassessed pending full-text review of PMID:30851065 (Delimitsou et al. 2019), which performed functional characterization of CHEK2 variants in a yeast system and may include p.Ser505Thr.
No de novo reports (PS2/PM6), no case-control enrichment data (PS4), no co-segregation data (PP1), and no trans-observation with a pathogenic variant (BP2) are available for this variant.
Applying generic ACMG/AMP 2015 combination rules (PMID:25741868) with PM2_Supporting (1 pathogenic point) and BP4_Supporting (1 benign point), the variant is classified as a Variant of Uncertain Significance (VUS), with the benign and pathogenic evidence effectively balancing each other. The CSPEC CHEK2 VCEP v1.0.0 (doc 522546466) did not provide machine-interpretable criteria beyond the raw ruleset.
No criteria match.
Met · 2
PM2 SupportingNM_007194.4:c.1513T>A is present at very low frequency in general population databases. gnomAD v2.1: 17/233,642 alleles (AF=0.00728%). gnomAD v4.1: 44/1,595,378 alleles (AF=0.00276%). The highest subpopulation frequency is in East Asians at 0.083% (v2.1, 15/17,996) and 0.078% (v4.1, 35/44,872), both below the 0.1% PM2 threshold for a gene with CHEK2-associated cancer predisposition. No homozygotes observed. Absent from gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=0.00728% (17/233642
- 0 hom)
- gnomAD v4.1: AF=0.00276% (44/1595378
- max subpop AF=0.083% (EAS v2.1)
- below 0.1% PM2 threshold.
Sources
BP4 SupportingMultiple lines of computational evidence unanimously predict no damaging effect for p.Ser505Thr. REVEL score is 0.018 (benign range), BayesDel score is -0.428 (benign range), and SpliceAI predicts no splice alteration (max delta = 0.00). These complementary in silico tools provide consistent evidence that the missense substitution is tolerated at the protein level. Details ▾Hide ▴
Evidence considered
- REVEL=0.018 (benign)
- BayesDel=-0.428 (benign)
- SpliceAI max delta=0.00 (no predicted splice impact).
Sources
Not met · 15 · evaluated, threshold not reached
PS2 No confirmed de novo occurrence of NM_007194.4:c.1513T>A has been reported in published literature or databases. Details ▾Hide ▴
Evidence considered
- No de novo data identified in ClinVar
- literature
- or database searches.
Still missing
- No published de novo reports for this variant exist.
PS4 No case-control study or statistical enrichment analysis specifically reporting an odds ratio for NM_007194.4:c.1513T>A in CHEK2-associated cancers (breast, ovarian, pancreatic, prostate) has been identified. gnomAD allele frequencies are low but do not by themselves establish case enrichment. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.00728% (17/233642)
- gnomAD v4.1 AF=0.00276% (44/1595378)
- no case-control comparison available.
Still missing
- No case-control study reporting variant enrichment in affected individuals.
Sources
PM6 No evidence for assumed de novo occurrence (i.e., de novo without confirmed paternity/maternity) has been identified for this variant in published literature or databases. Details ▾Hide ▴
Evidence considered
- No assumed de novo reports identified.
Still missing
- No published evidence of de novo occurrence.
PP1 No co-segregation data with disease in multiple affected family members has been reported for NM_007194.4:c.1513T>A. Details ▾Hide ▴
Evidence considered
- No published co-segregation studies identified.
Still missing
- No family segregation data available.
PP3 Multiple in silico prediction tools uniformly predict a benign impact for p.Ser505Thr. REVEL score is 0.018 (well below the pathogenic threshold of ~0.5, firmly in benign range). BayesDel score is -0.428 (benign range, below pathogenic threshold). SpliceAI delta score is 0.00 (no predicted splice alteration). No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL=0.018 (benign)
- BayesDel=-0.428 (benign)
- SpliceAI max delta=0.00 (no splice impact)
- HCI prior not available for CHEK2.
Sources
PP4 Insufficient clinical data demonstrating that the variant-carrier phenotype or family history is highly specific for CHEK2-associated disease. No detailed clinical case descriptions identifying this variant in patients with CHEK2-specific tumor spectrum and family history are available. Details ▾Hide ▴
Evidence considered
- No detailed clinical case descriptions with CHEK2-specific phenotype and variant confirmation available.
Still missing
- No clinical case reports with detailed phenotype and family history data.
PP5 No reputable source (e.g., expert panel, clinical guideline) has classified NM_007194.4:c.1513T>A as pathogenic or likely pathogenic. ClinVar consensus is Likely benign from multiple clinical laboratories. The ClinGen CHEK2 VCEP has not issued a classification for this variant. Details ▾Hide ▴
Evidence considered
- ClinVar: Likely benign (4 labs)
- Uncertain significance (1 lab)
- likely benign (1 lab)
- no expert panel classification
- no pathogenic assertion from reputable source.
Sources
BA1 The maximum population minor allele frequency for NM_007194.4:c.1513T>A is 0.083% in East Asians (gnomAD v2.1) and 0.078% in East Asians (gnomAD v4.1), both well below the 1% BA1 threshold. The variant is not common enough to meet BA1. Details ▾Hide ▴
Evidence considered
- Max AF=0.083% (EAS v2.1) and 0.078% (EAS v4.1)
- both <1% BA1 threshold.
Sources
BS1 The maximum population allele frequency of 0.083% in East Asians (gnomAD v2.1) is below the 0.3% BS1 threshold. The variant is not sufficiently common in control populations to meet BS1. Details ▾Hide ▴
Evidence considered
- Max AF=0.083% (EAS v2.1) and 0.078% (EAS v4.1)
- both <0.3% BS1 threshold.
Sources
BS2 No observation of NM_007194.4:c.1513T>A in a homozygous state in gnomAD (0 homozygotes across v2.1 and v4.1) nor reported in trans with a known pathogenic CHEK2 variant in a healthy adult. Insufficient evidence to satisfy BS2. Details ▾Hide ▴
Evidence considered
- 0 homozygotes in gnomAD v2.1 and v4.1
- no reported co-occurrence in trans with pathogenic CHEK2 variant in a healthy individual.
Still missing
- No homozygous or compound heterozygous observation in a healthy adult.
Sources
BS4 No co-segregation or family data are available demonstrating lack of segregation of NM_007194.4:c.1513T>A with disease in affected families. Details ▾Hide ▴
Evidence considered
- No family segregation data available to evaluate non-segregation.
Still missing
- No family data showing variant does not segregate with disease.
BP1 BP1 is applicable to missense variants in genes where primarily truncating variants are known to cause disease. While CHEK2 has well-established pathogenic truncating variants (e.g., 1100delC), it also has recognized pathogenic missense variants. Therefore, BP1 does not apply. Details ▾Hide ▴
Evidence considered
- CHEK2 has both truncating and missense pathogenic variants
- BP1 not applicable.
BP2 No observation of NM_007194.4:c.1513T>A in trans with a known pathogenic CHEK2 variant has been reported in the literature or databases. Details ▾Hide ▴
Evidence considered
- No reported trans co-occurrence with a pathogenic CHEK2 variant.
Still missing
- No observation of variant in trans with a known pathogenic CHEK2 variant.
BP5 No case has been identified where NM_007194.4:c.1513T>A is observed in an individual with an alternate molecular basis for disease. There is no evidence to support BP5. Details ▾Hide ▴
Evidence considered
- No reported case with an alternate molecular disease explanation.
Still missing
- No data on alternate molecular basis in variant carriers.
BP6 No expert panel or other highly reputable source has classified NM_007194.4:c.1513T>A as benign. While multiple clinical laboratories have classified this variant as Likely benign in ClinVar, the review status is 'criteria provided, single submitter' without expert panel consensus. BP6 requires a reputable source reporting the variant as benign with evidence unavailable for independent evaluation; Likely benign from individual clinical laboratories does not meet this threshold. Details ▾Hide ▴
Evidence considered
- ClinVar: Likely benign from 4 clinical labs
- no expert panel benign classification
- review status is single submitter
- not meeting BP6 reputable-source threshold.
Sources
Not assessed · 3 · no assessment recorded
PS3 Functional data for NM_007194.4:c.1513T>A (p.Ser505Thr) could not be confirmed. PMID:30851065 (Delimitsou et al. 2019, functional characterization of CHEK2 variants in yeast) may contain functional assessment of this variant, but full-text verification is unavailable in the case directory. OncoKB reports no variant-specific reviewed functional evidence. Details ▾Hide ▴
Evidence considered
- PMID:30851065 abstract mentions CHEK2 variant functional assessment in yeast
- variant-specific inclusion unconfirmed without full-text.
Still missing
- Full-text of PMID:30851065 required to confirm whether p.Ser505Thr was functionally assessed.
Sources
PM1 Residue Ser505 lies within the CHEK2 protein kinase domain (approximately residues 220-540). However, the CHEK2 VCEP v1.0.0 does not provide machine-readable domain-level PM1 specifications for critical functional domains, and gnomAD shows a subpopulation frequency of 0.083% in East Asians (v2.1), indicating some population tolerance for missense variation in this region. Without explicit VCEP-defined critical domain boundaries and benign-variation-free thresholds, PM1 cannot be cleanly applied under the current framework. Details ▾Hide ▴
Evidence considered
- Ser505 in kinase domain
- CHEK2 VCEP v1.0.0 lacks explicit PM1 domain specifications
- EAS subpopulation AF=0.083%.
Still missing
- CHEK2 VCEP v1.0.0 does not define specific critical domains for PM1
- manual expert review of domain constraint needed.
Sources
BS3 Normal functional evidence for NM_007194.4:c.1513T>A (p.Ser505Thr) could not be confirmed. No variant-specific benign functional data was identified in OncoKB. PMID:30851065 (Delimitsou et al. 2019) performed functional characterization of CHEK2 variants in a yeast system but full-text is unavailable for confirmation of whether p.Ser505Thr was included and showed wild-type-like function. Details ▾Hide ▴
Evidence considered
- PMID:30851065 is a relevant functional study (CHEK2 variants in yeast) but variant-specific inclusion cannot be confirmed without full-text.
Still missing
- Full-text of PMID:30851065 needed to verify whether p.Ser505Thr was assessed and demonstrated normal function.
Sources
Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_007194.4:c.1513T>A is a missense variant (p.Ser505Thr) in exon 14 of CHEK2, not a null variant (nonsense, frameshift, canonical ±1,2 splice consensus, initiation codon loss, or exon deletion). PVS1 is not applicable to missense variants. Details ▾Hide ▴
Evidence considered
- Variant class: missense
- PVS1 bucket: other
- generic PVS1 framework not applicable per ClinGen SVI recommendations (PMC6185798).
Sources
PS1 N/ANo previously classified pathogenic variant with the exact same amino acid change (p.Ser505Thr) at this residue has been identified in ClinVar or the literature. Details ▾Hide ▴
Evidence considered
- No same-residue same-AA pathogenic comparator identified.
PM5 N/ANo pathogenic variant at the same residue (Ser505) with a different amino acid substitution has been identified in ClinVar or literature. PM5 candidate harvesting returned zero candidates at this codon. Details ▾Hide ▴
Evidence considered
- Zero same-residue comparator candidates per PM5 candidate assessment.
PP2 N/APP2 applies to genes where missense variants are a common mechanism of disease and benign missense variation is rare. CHEK2 has numerous missense variants in gnomAD with measurable population frequencies, and pathogenic CHEK2 variants include both truncating and missense types. PP2 is not appropriate for CHEK2 under generic ACMG/AMP guidelines. Details ▾Hide ▴
Evidence considered
- CHEK2 tolerates missense variation in population databases
- not a gene with exclusively pathogenic missense mechanism.
Sources
BP7 N/ANM_007194.4:c.1513T>A is a missense variant (p.Ser505Thr), not a synonymous/silent variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense
- BP7 is specific to synonymous/silent variants.
PS5 N/ANo previously classified pathogenic variant with a different amino acid change at residue 505 has been identified. PM5 candidate assessment confirmed no same-residue comparators. Details ▾Hide ▴
Evidence considered
- No same-residue pathogenic comparator identified for PS5 application.
Identifiers
- Gene
- CHEK2
- Transcript
- NM_007194.4
- Coding (HGVS c.)
- NM_007194.4:c.1513T>A
- Protein (HGVS p.)
- NP_009125.1:p.(Ser505Thr)
- GRCh38
- chr22:28689164 A>T
- GRCh37
- chr22:29085152 A>T
- ClinVar
- 182441
Gene diagram
Every interpreted variant in CHEK2, mapped onto the exon structure of NM_007194.4. Select a row to find it on the plot.
CHEK2NM_007194.4
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 CHEK2
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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
44 / 1,595,378 alleles
AF 2.76e-05 · 0 homozygotes · FAF 0.000576
gnomAD v2.1
17 / 233,642 alleles
AF 7.28e-05 · 0 homozygotes · FAF 0.000514
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 2.8e-05 · 44 / 1,595,378 alleles · 0 hom · FAF 0.00058
| East Asian35 / 44,872 | 0.00078 |
| Remaining individuals7 / 62,170 | 0.00011 |
| Admixed American2 / 59,982 | 3.3e-05 |
0 alternate alleles recorded in 7 other groups: European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish).
gnomAD v2.1
AF 7.3e-05 · 17 / 233,642 alleles · 0 hom · FAF 0.00051
| East Asian15 / 17,996 | 0.00083 |
| Admixed American2 / 34,358 | 5.8e-05 |
0 alternate alleles recorded in 6 other groups: African/African American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 2.75797e-05; MAF= 0.00276%, 44/1595378 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000779996; MAF= 0.07800%, 35/44872 alleles, homozygotes = 0); grpmax FAF= 0.00057582.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.27609e-05; MAF= 0.00728%, 17/233642 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000833519; MAF= 0.08335%, 15/17996 alleles, homozygotes = 0); grpmax FAF= 0.00051369.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.018
- BayesDel
- -0.428
How the predictions were used
BP4 SupportingMultiple lines of computational evidence unanimously predict no damaging effect for p.Ser505Thr. REVEL score is 0.018 (benign range), BayesDel score is -0.428 (benign range), and SpliceAI predicts no splice alteration (max delta = 0.00). These complementary in silico tools provide consistent evidence that the missense substitution is tolerated at the protein level. Details ▾Hide ▴
Evidence considered
- REVEL=0.018 (benign)
- BayesDel=-0.428 (benign)
- SpliceAI max delta=0.00 (no predicted splice impact).
Sources
PP3 Multiple in silico prediction tools uniformly predict a benign impact for p.Ser505Thr. REVEL score is 0.018 (well below the pathogenic threshold of ~0.5, firmly in benign range). BayesDel score is -0.428 (benign range, below pathogenic threshold). SpliceAI delta score is 0.00 (no predicted splice alteration). No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL=0.018 (benign)
- BayesDel=-0.428 (benign)
- SpliceAI max delta=0.00 (no splice impact)
- HCI prior not available for CHEK2.
Sources
BP7 N/ANM_007194.4:c.1513T>A is a missense variant (p.Ser505Thr), not a synonymous/silent variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense
- BP7 is specific to synonymous/silent variants.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.018. BayesDel score = -0.428192.
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 15942682 ↗Aberrations of the CHK2 gene are rare in pediatric solid tumors.Chen YY et al. · 2005No paper-specific finding is recorded.
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PMID 23918944 ↗Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.No paper-specific finding is recorded.
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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 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.No paper-specific finding is recorded.
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PMID 30851065 ↗Functional characterization of CHEK2 variants in a Saccharomyces cerevisiae system.Delimitsou A et al. · 2019No paper-specific finding is recorded.
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PMID 32566746 ↗Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome.No paper-specific finding is recorded.
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PMID 12692171 ↗American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.No paper-specific finding is recorded.
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.No 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
44 / 1,595,378 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
4 Likely benign · 1 Uncertain significance · 1 likely benign
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/522546466
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/182441/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/22-29085152-A-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr22-28689164-A-T?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007194.4%3Ac.1513…
- OncoKB ↗www.oncokb.org/gene/CHEK2/S505T
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=CHEK2+c.1513T%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= 2.75797e-05; MAF= 0.00276%, 44/1595378 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000779996; MAF= 0.07800%, 35/44872 alleles, homozygotes = 0); grpmax FAF= 0.00057582.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.27609e-05; MAF= 0.00728%, 17/233642 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000833519; MAF= 0.08335%, 15/17996 alleles, homozygotes = 0); grpmax FAF= 0.00051369.
ClinVar
This variant has been reported in ClinVar as Likely benign (4 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as likely benign (1 clinical laboratory). (ClinVarID = 182441)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.018. BayesDel score = -0.428192.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. CHEK2, an intracellular kinase involved in control of the cell cycle, is altered in various cancer types.
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.