About CHEK2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
CHEK2 c.751A>T, p.(Ile251Phe)
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: 2
Benign evidence criteria: 1
Pathogenic criteria applied · 2
PM1Moderate
PM1 · moderate
The variant alters residue Ile251 in the CHEK2 kinase domain (residues ~220–500), a well-established critical functional domain essential for CHEK2 kinase activity and DNA damage signaling. Missense substitutions in the kinase domain have been shown to abolish CHEK2 function.
PM2Supporting
PM2 · supporting
The variant is present at an extremely low frequency in population databases: gnomAD v2.1 AF=0.00177% (5/282,756 alleles), gnomAD v4.1 AF=0.00328% (53/1,613,926 alleles), and absent from gnomAD-Canada. These frequencies are well below the PM2 threshold of 0.1%.
Benign criteria applied · 1
BS4Supporting
BS4 · supporting
In the familial prostate cancer family reported by Dong et al. (PMID:12533788), the c.751A>T variant was detected in only 1 of 2 affected brothers, demonstrating lack of segregation with disease. This represents a non-segregation event in affected family members supporting a benign interpretation.
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: PM1 moderate, PM2 supporting, BS4 supporting benign; combination = 1 moderate + 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
53 / 1,613,926 alleles
gnomAD v4.1: 53 / 1,613,926 alleles. Recorded AF 3.28392e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.76831e-05; MAF= 0.00177%, 5/282756 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.87177e-05; MAF= 0.00387%, 5/129140 alleles, homozygotes = 0); grpmax FAF= 5.239e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016286644951140066, 3/18420 alleles, homozygotes = 0).
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
18 reported laboratory submissions
15 Uncertain significance · 2 Likely pathogenic · 1 likely pathogenic. ClinVar API review status: criteria provided, conflicting classifications.
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.
29 criteria with recorded statuses: 3 met · 21 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
PM1 (moderate) is met: the variant alters Ile251 in the CHEK2 kinase domain, a well-established critical functional domain.
PM2 (supporting) is met: the variant is present at extremely low frequency in population databases (gnomAD v2.1 AF=0.00177%, gnomAD v4.1 AF=0.00328%).
BS4 (supporting benign) is met: the variant demonstrated lack of segregation in a familial prostate cancer family, where it was detected in only 1 of 2 affected brothers.
The variant has been observed in individual cases of familial prostate cancer (1/298) and hereditary breast cancer (1/507) but has not demonstrated statistically significant case-control enrichment.
No variant-specific functional studies have been performed for p.Ile251Phe. In silico predictions are mixed: REVEL=0.426, BayesDel=0.178, PolyPhen-2=Probably damaging, SIFT=Tolerated.
ClinVar classification is Uncertain significance (15 VUS, 3 Likely pathogenic submissions). No expert panel review has been performed.
With one moderate pathogenic criterion (PM1), one supporting pathogenic criterion (PM2), and one supporting benign criterion (BS4), the evidence is equivocal and the variant remains a Variant of Uncertain Significance (VUS).
No criteria match.
Met · 3
PM1 ModerateThe variant alters residue Ile251 in the CHEK2 kinase domain (residues ~220–500), a well-established critical functional domain essential for CHEK2 kinase activity and DNA damage signaling. Missense substitutions in the kinase domain have been shown to abolish CHEK2 function. Details ▾Hide ▴
Evidence considered
- Located in the kinase domain of CHEK2 (exon 6). The kinase domain is a well-established critical functional domain involved in phosphorylation of downstream targets including p53 and BRCA1.
Sources
PM2 SupportingThe variant is present at an extremely low frequency in population databases: gnomAD v2.1 AF=0.00177% (5/282,756 alleles), gnomAD v4.1 AF=0.00328% (53/1,613,926 alleles), and absent from gnomAD-Canada. These frequencies are well below the PM2 threshold of 0.1%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 5/282
- 756 alleles (AF=0.00177%)
- gnomAD v4.1: 53/1
- 613
- 926 alleles (AF=0.00328%)
- gnomAD-Canada: absent (0 alleles)
Sources
BS4 SupportingIn the familial prostate cancer family reported by Dong et al. (PMID:12533788), the c.751A>T variant was detected in only 1 of 2 affected brothers, demonstrating lack of segregation with disease. This represents a non-segregation event in affected family members supporting a benign interpretation. Details ▾Hide ▴
Evidence considered
- Variant found in only 1 of 2 affected brothers in a familial prostate cancer family (PMID:12533788)
- indicating lack of segregation.
Sources
Not met · 21 · evaluated, threshold not reached
PVS1 This variant is a missense substitution (c.751A>T, p.Ile251Phe) and does not fall into a null-variant category (nonsense, frameshift, canonical ±1,2 splice site, initiation codon, or exon deletion). PVS1 is not applicable to missense variants under generic ACMG/AMP 2015 rules. Details ▾Hide ▴
Evidence considered
- Missense variant in exon 6
- not a null variant.
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PS1 No evidence that a different nucleotide change at c.751 resulting in the same amino acid alteration (p.Ile251Phe) has been established as pathogenic. Details ▾Hide ▴
No further detail was recorded.
PS2 No de novo observation has been reported for this variant. Details ▾Hide ▴
No further detail was recorded.
PS3 No variant-specific functional assay has been performed for p.Ile251Phe. The kinase activity assay in Desrichard et al. (PMID:22114986) tested 11 CHEK2 missense variants but did not include p.Ile251Phe. Dong et al. (PMID:12533788) performed western blot analysis for frameshift mutations only; missense variants were used as controls showing normal protein levels but p.Ile251Phe was not individually characterized. Details ▾Hide ▴
Evidence considered
- No direct functional assay for p.Ile251Phe. Kinase assay in PMID:22114986 did not include this variant.
Still missing
- No variant-specific functional data exist for p.Ile251Phe.
Sources
PS4 The variant has been observed in individual cases across two studies (1/298 familial prostate cancer in Dong et al. 2003, 1/507 hereditary breast cancer cases in Desrichard et al. 2011) but has not been subjected to a statistical case-control analysis demonstrating significant enrichment over population controls. Individual case observations do not meet the threshold for PS4. Details ▾Hide ▴
Evidence considered
- Observed in 1 familial prostate cancer case (PMID:12533788)
- 1 HBC case (PMID:22114986)
- and listed as VUS in a CRC cohort (PMID:28135145).
Still missing
- No case-control study with statistical power to demonstrate enrichment.
Sources
PM5 No pathogenic missense variant at the same amino acid residue (Ile251) has been identified in ClinVar or the literature. The automated PM5 candidate search did not yield any same-residue comparator variants. Details ▾Hide ▴
Evidence considered
- No same-residue pathogenic missense comparator identified.
Sources
pm5_candidates
PM6 No de novo observation has been reported for this variant. PM6 requires a de novo observation with confirmed maternity and paternity. Details ▾Hide ▴
No further detail was recorded.
PP1 In the familial prostate cancer family reported by Dong et al. (PMID:12533788), the A751T variant was detected in only 1 of 2 affected brothers tested, demonstrating lack of co-segregation with disease in the family. Details ▾Hide ▴
Evidence considered
- Variant found in only 1 of 2 affected brothers in a familial prostate cancer family (PMID:12533788
- family 8 or 9).
Sources
PP2 Gene-level missense constraint data are not available to confirm that CHEK2 has a low rate of benign missense variation. CHEK2 has multiple reported pathogenic missense variants (e.g., p.Ile157Thr, p.Arg145Trp, p.Arg117Gly), which argues against a gene-wide application of PP2. Details ▾Hide ▴
Still missing
- No gene-level missense constraint Z-score available.
PP3 Computational evidence is mixed and does not meet the threshold for multiple lines supporting a deleterious effect. REVEL score is 0.426 (below 0.5 threshold), BayesDel score is 0.178 (below deleterious threshold), and SpliceAI predicts no splicing impact (max delta=0.00). PolyPhen-2 predicted 'Probably damaging' in Desrichard et al. (PMID:22114986), but Align-GVGD class C0 and SIFT predicted 'Tolerated.' The preponderance of in silico tools does not converge on a deleterious prediction. Details ▾Hide ▴
Evidence considered
- REVEL=0.426
- BayesDel=0.178
- SpliceAI max delta=0.00
- PolyPhen-2=Probably damaging
- SIFT=Tolerated
- Align-GVGD=C0 (PMID:22114986)
Sources
PP4 The variant has been observed in patients with prostate cancer, breast cancer, and colorectal cancer — phenotypes that are not highly specific for a single genetic etiology. CHEK2-related cancer predisposition has a broad and overlapping phenotype spectrum that does not satisfy PP4's requirement for a highly specific phenotype. Details ▾Hide ▴
No further detail was recorded.
PP5 The variant is classified as 'Uncertain significance' overall in ClinVar (ClinVarID 128086). While 3 of 20 submissions classified it as 'Likely pathogenic,' the majority (15 submissions) classified it as VUS. No expert panel has reviewed this variant. PP5 requires a reputable source reporting the variant as pathogenic, which is not met by the current ClinVar consensus. Details ▾Hide ▴
Evidence considered
- ClinVar: Uncertain significance overall
- 15 VUS
- 3 Likely pathogenic submissions.
- No expert panel classification.
Sources
BA1 The maximum population allele frequency is 0.00387% (gnomAD v2.1, European non-Finnish), far below the BA1 threshold of 1%. Details ▾Hide ▴
Evidence considered
- gnomAD max AF: 0.00387% (European non-Finnish
- v2.1)
- grpmax FAF: 5.239e-05.
Sources
BS1 The population allele frequency (gnomAD v2.1 AF=0.00177%, gnomAD v4.1 AF=0.00328%) is well below the BS1 threshold of 0.3%. Details ▾Hide ▴
BS2 No homozygous individuals have been observed, and there are no confirmed observations of this variant in healthy adult individuals with documented normal phenotype to satisfy BS2. Details ▾Hide ▴
Evidence considered
- gnomAD: 0 homozygotes. No healthy-adult confirmation studies.
BS3 No variant-specific functional assay demonstrating a benign effect has been performed for p.Ile251Phe. The kinase assay in Desrichard et al. did not include this variant. Dong et al. showed normal CHEK2 protein levels for pooled missense variants by western blot, but p.Ile251Phe was not individually characterized. This does not constitute well-established functional evidence of no damaging effect. Details ▾Hide ▴
Evidence considered
- No variant-specific benign functional assay available.
Still missing
- No functional characterization of p.Ile251Phe.
Sources
BP1 CHEK2 has multiple established pathogenic missense variants (e.g., p.Ile157Thr, p.Arg145Trp, p.Arg117Gly, p.Thr476Met) in addition to truncating variants. BP1 is applicable only to genes where the primary disease mechanism is truncating variants, which is not the case for CHEK2. Details ▾Hide ▴
Evidence considered
- CHEK2 has known pathogenic missense variants (PMID:22114986).
Sources
BP2 No evidence of this variant being observed in trans with a known pathogenic CHEK2 variant, or in cis with a known pathogenic variant in any inheritance pattern. Details ▾Hide ▴
No further detail was recorded.
BP4 Computational evidence does not converge on a benign prediction. PolyPhen-2 predicted 'Probably damaging' (PMID:22114986), while REVEL (0.426) and BayesDel (0.178) are in the indeterminate range. SpliceAI predicts no splicing impact. The in silico evidence is mixed and does not meet the 'multiple lines suggesting no impact' threshold for BP4. Details ▾Hide ▴
Evidence considered
- REVEL=0.426 (indeterminate)
- BayesDel=0.178 (indeterminate)
- SpliceAI=0.00
- PolyPhen-2=Probably damaging.
Sources
BP5 No evidence that this variant has been found in a case with an alternate molecular basis for disease. BP5 requires observation in an individual with a confirmed alternate genetic cause for the same phenotype. Details ▾Hide ▴
No further detail was recorded.
BP6 No reputable source has classified this variant as benign. ClinVar consensus is 'Uncertain significance.' BP6 requires a reputable source reporting the variant as benign with unavailable evidence. Details ▾Hide ▴
Evidence considered
- ClinVar: Uncertain significance
- no benign classification from any source.
Sources
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PM3 N/APM3 applies to recessive disorders where the variant is detected in trans with a pathogenic variant. CHEK2-related cancer predisposition is autosomal dominant. Details ▾Hide ▴
No further detail was recorded.
PM4 N/APM4 applies to protein length changes due to in-frame deletions/insertions or stop-loss variants. This is a missense substitution. Details ▾Hide ▴
No further detail was recorded.
BP3 N/ABP3 applies to in-frame deletions/insertions in repetitive regions; this is a missense substitution. Details ▾Hide ▴
No further detail was recorded.
BP7 N/AThis is a missense variant (c.751A>T, p.Ile251Phe). BP7 applies only to synonymous (silent) variants with no predicted splicing impact. Details ▾Hide ▴
No further detail was recorded.
PS5 N/APS5 is not a standard ACMG/AMP 2015 criterion and no VCEP-specific PS5 rule has been defined for CHEK2. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- CHEK2
- Transcript
- NM_007194.4
- Coding (HGVS c.)
- NM_007194.4:c.751A>T
- Protein (HGVS p.)
- NP_009125.1:p.(Ile251Phe)
- GRCh38
- chr22:28711950 T>A
- GRCh37
- chr22:29107938 T>A
- ClinVar
- 128086
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
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in CHEK2
—
Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
53 / 1,613,926 alleles
AF 3.28e-05 · 0 homozygotes · FAF 3.5e-05
gnomAD v2.1
5 / 282,756 alleles
AF 1.77e-05 · 0 homozygotes · FAF 5.24e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 3.3e-05 · 53 / 1,613,926 alleles · 0 hom · FAF 3.5e-05
| European (non-Finnish)53 / 1,179,970 | 4.5e-05 |
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 v2.1
AF 1.8e-05 · 5 / 282,756 alleles · 0 hom · FAF 5.2e-05
| European (non-Finnish)5 / 129,140 | 3.9e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.28392e-05; MAF= 0.00328%, 53/1613926 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.49164e-05; MAF= 0.00449%, 53/1179970 alleles, homozygotes = 0); grpmax FAF= 3.503e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.76831e-05; MAF= 0.00177%, 5/282756 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.87177e-05; MAF= 0.00387%, 5/129140 alleles, homozygotes = 0); grpmax FAF= 5.239e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016286644951140066, 3/18420 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.426
- BayesDel
- 0.178
How the predictions were used
PP3 Computational evidence is mixed and does not meet the threshold for multiple lines supporting a deleterious effect. REVEL score is 0.426 (below 0.5 threshold), BayesDel score is 0.178 (below deleterious threshold), and SpliceAI predicts no splicing impact (max delta=0.00). PolyPhen-2 predicted 'Probably damaging' in Desrichard et al. (PMID:22114986), but Align-GVGD class C0 and SIFT predicted 'Tolerated.' The preponderance of in silico tools does not converge on a deleterious prediction. Details ▾Hide ▴
Evidence considered
- REVEL=0.426
- BayesDel=0.178
- SpliceAI max delta=0.00
- PolyPhen-2=Probably damaging
- SIFT=Tolerated
- Align-GVGD=C0 (PMID:22114986)
Sources
BP4 Computational evidence does not converge on a benign prediction. PolyPhen-2 predicted 'Probably damaging' (PMID:22114986), while REVEL (0.426) and BayesDel (0.178) are in the indeterminate range. SpliceAI predicts no splicing impact. The in silico evidence is mixed and does not meet the 'multiple lines suggesting no impact' threshold for BP4. Details ▾Hide ▴
Evidence considered
- REVEL=0.426 (indeterminate)
- BayesDel=0.178 (indeterminate)
- SpliceAI=0.00
- PolyPhen-2=Probably damaging.
Sources
BP7 N/AThis is a missense variant (c.751A>T, p.Ile251Phe). BP7 applies only to synonymous (silent) variants with no predicted splicing impact. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.426. BayesDel score = 0.177609.
8 paper records listed. 2 cited in the classification.
Cited in the classification
-
PMID 12533788 ↗Mutations in CHEK2 associated with prostate cancer risk.Dong X et al. · 2003 FebA751T (Ile251Phe) identified as a germline CHEK2 missense mutation in 1 of 298 familial prostate cancer probands and absent in 423 unaffected controls. The variant was found in only 1 of 2 affected brothers in the family tested for segregation. The missense variant was not individually characterized in functional assays; western blot analysis of pooled missense mutations showed normal CHEK2 protein levels.→ PM1 → BS4 Names this variant
Source detail
three were missense mutations—one in exon 3 (T470C, Ile157Thr) and two in exon 5 (G715A, Glu239Lys and A751T, Ile251Phe)
Location Table 1 (mutation #13); Results paragraphs 1, 3, 5; Figure 3C
Context DHPLC mutation screening followed by Sanger sequencing; western blot analysis in EBV-transformed lymphoblastoid cell lines
-
PMID 22114986 ↗CHEK2 contribution to hereditary breast cancer in non-BRCA families.Desrichard A et al. · 2011751A>T (Ile251Phe) identified in 1 of 507 non-BRCA hereditary breast cancer cases and absent in 513 controls. In silico analysis: Align-GVGD class C0, SIFT tolerated (score 2.04), PolyPhen-2 probably damaging. Classified as 'probably deleterious' by study criteria. This variant was not included in the in vitro kinase activity assay.→ PM1 Names this variant
Source detail
751A > T [ 23 ] Ile251Phe 6 Kinase - C0 2.04 Tolerated Probably damaging Probably deleterious
Location Table 1 (case population mutations); Results paragraph 1
Context In silico prediction only; variant was not among the 11 variants tested in the Omnia in vitro kinase activity assay using recombinant Flag-CHEK2 expressed in E. coli
Other recorded publications
-
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.This is the ACMG/AMP 2015 standards and guidelines paper for sequence variant interpretation. It does not discuss any specific CHEK2 variant or NM_007194.4:c.751A>T.Does not name this variant
-
PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Describes a standardized DNA variant scoring system for pathogenicity assessment in Mendelian disorders. Does not discuss any specific CHEK2 variant or NM_007194.4:c.751A>T.Does not name this variant
-
PMID 27498913 ↗Monogenic and polygenic determinants of sarcoma risk: an international genetic study.Ballinger ML et al. · 2016Targeted exon sequencing study of 72 cancer genes in 1162 sarcoma patients. Reports enrichment of pathogenic variants in TP53, ATM, ATR, BRCA2, and ERCC2. CHEK2 is mentioned at gene level but NM_007194.4:c.751A>T was not identified in this paper.Does not name this variant
-
PMID 27978560 ↗Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer.Pearlman R et al. · 2017Study of germline cancer susceptibility gene mutations in 450 patients with early-onset colorectal cancer using a 25-gene panel. CHEK2 is included in the panel but NM_007194.4:c.751A>T is not specifically reported in the results.Does not name this variant
-
PMID 28135145 ↗Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.Yurgelun MB et al. · 2017Multigene panel testing of 1,058 colorectal cancer patients. NM_007194.4:c.751A>T (p.Ile251Phe) is listed in the appendix among variants of uncertain significance (sample COLB5425-3). Two CHEK2 pathogenic mutations were reported in the main text (3.6% of participants); this variant was not among them.Names this variant
Quoted passage
c.751A.T (p.Ile251Phe)
Appendix Table A4 (variants of uncertain significance), line 3752
-
PMID 28843361 ↗Germline Mutations in DNA Repair Genes in Lung Adenocarcinoma.Study of germline mutations in DNA repair genes (ATM, BRCA2, CHEK2, EGFR, PARK2, TERT, TP53, YAP1) in lung adenocarcinoma. CHEK2 is discussed at gene level in the context of GWAS associations but NM_007194.4:c.751A>T was not identified in this paper.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
53 / 1,613,926 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
15 Uncertain significance · 2 Likely 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/522546466
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/128086/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/22-29107938-T-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr22-28711950-T-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/22-28711950-T-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007194.4%3Ac.751A…
- OncoKB ↗www.oncokb.org/gene/CHEK2/I251F
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=CHEK2+c.751A%3ET
- 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= 3.28392e-05; MAF= 0.00328%, 53/1613926 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.49164e-05; MAF= 0.00449%, 53/1179970 alleles, homozygotes = 0); grpmax FAF= 3.503e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.76831e-05; MAF= 0.00177%, 5/282756 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.87177e-05; MAF= 0.00387%, 5/129140 alleles, homozygotes = 0); grpmax FAF= 5.239e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016286644951140066, 3/18420 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Uncertain significance (15 clinical laboratories) and as Likely pathogenic (2 clinical laboratories) and as likely pathogenic (1 clinical laboratory). (ClinVarID = 128086)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.426. BayesDel score = 0.177609.
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.