About TP53
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TP53 c.684C>G, p.(Asp228Glu)
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 TP53 VCEP v2.4.0. 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: 2
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
The variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0, meeting the TP53 VCEP PM2_Supporting threshold of allele frequency <0.00003 (0.003%).
Benign criteria applied · 2
BS3Strong
BS3 · strong
The TP53 VCEP Functional-worksheet pre-assigns BS3 (strong benign functional evidence) for p.Asp228Glu. The variant is Functional in the Kato et al. (PMID:12826609) systematic assay and shows no loss of function (noLOF) across all eligible assays: Giacomelli et al. (PMID:30224644), Kotler et al. (PMID:29979965), and Kawaguchi et al. This meets the VCEP BS3 rule: 'Functional on Kato et al. data AND no loss of function (LOF) by the majority of available eligible assays.'
BP4Moderate
BP4 · moderate
The variant has a BayesDel score of -0.133538, which is ≤ -0.008, and SpliceAI predicts no splicing impact (max delta = 0.00, which is <0.2). The aGVGD class is C0 (not C65). Per the TP53 VCEP PP3-BP4 missense flowchart: BayesDel ≤ -0.008 + no predicted splicing differences + not C65 = BP4_Moderate. The VCEP PP3-BP4-codes spreadsheet confirms this with a pre-assigned code of BP4_moderate.
Recorded classification: Likely benign
Total points: PM2_Supporting (+1) + BS3 (-4) + BP4_Moderate (-2) = -5. Per the TP53 VCEP v2.4.0 Tavtigian Bayesian point-based framework, a score of -5 falls in the Likely Benign range (Rule4: -6 to -2).
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
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
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
5 Uncertain significance · 1 Likely benign.
Context only
ClinVar ↗
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.
COSMIC
Cancer Hotspots
Somatic evidence
6 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV52662428, n = 6 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen TP53 VCEP v2.4.0, with the data and sources behind each one.
29 criteria with recorded statuses: 3 met · 5 not met · 8 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
NM_000546.5:c.684C>G (p.Asp228Glu) is a missense variant in exon 7 of TP53.
The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada (PM2_Supporting; +1 point).
Functional evidence from the TP53 VCEP Functional-worksheet demonstrates the variant retains wild-type-like function: Kato et al. assay shows Functional activity, and all eligible assays (Giacomelli, Kotler, Kawaguchi) report no loss of function (BS3; -4 points).
In silico evidence supports a benign interpretation: BayesDel score is -0.133538 (Class C0), and SpliceAI predicts no splicing impact (max delta 0.00). The VCEP PP3-BP4-codes spreadsheet assigns BP4_moderate (-2 points).
Codon 228 is not among the VCEP-defined hotspot codons (175, 245, 248, 249, 273, 282), and the variant is not listed in cancerhotspots.org; PM1 is not met.
PP3 is not met per VCEP in silico flowchart: BayesDel score does not meet the ≥0.16 threshold and aGVGD class is C0.
PS3 is not met: the functional evidence favors a benign interpretation; the VCEP pre-assigned code is BS3, not PS3.
Total points: PM2_Supporting (+1) + BS3 (-4) + BP4_Moderate (-2) = -5. Per the Tavtigian Bayesian point-based framework (TP53 VCEP v2.4.0), a score of -5 falls in the Likely Benign range (-6 to -2).
This variant has been reported in ClinVar as Uncertain significance by 5 clinical laboratories and as Likely benign by 1 clinical laboratory (ClinVar ID: 926556).
COSMIC reports 6 somatic occurrences (COSV52662428). OncoKB classifies the variant as Likely Oncogenic with likely loss-of-function effect, which is inconsistent with the VCEP functional data showing retained function; the VCEP functional worksheet takes precedence for germline classification.
No de novo, segregation, proband, or case-control data are available; PS2, PS4, PP1, PP4, BS2, and BS4 remain unassessed.
No criteria match.
Met · 3
PM2 SupportingThe variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0, meeting the TP53 VCEP PM2_Supporting threshold of allele frequency <0.00003 (0.003%). Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (exomes). Absent from gnomAD v4.1 (exomes). Absent from gnomAD-Canada v1.0 (genomes).
Sources
BS3 StrongThe TP53 VCEP Functional-worksheet pre-assigns BS3 (strong benign functional evidence) for p.Asp228Glu. The variant is Functional in the Kato et al. (PMID:12826609) systematic assay and shows no loss of function (noLOF) across all eligible assays: Giacomelli et al. (PMID:30224644), Kotler et al. (PMID:29979965), and Kawaguchi et al. This meets the VCEP BS3 rule: 'Functional on Kato et al. data AND no loss of function (LOF) by the majority of available eligible assays.' Details ▾Hide ▴
Evidence considered
- VCEP Functional-worksheet: D228E → BS3. Kato: Functional. Giacomelli: noLOF. Kotler: noLOF. Kawaguchi: noLOF.
Sources
BP4 ModerateThe variant has a BayesDel score of -0.133538, which is ≤ -0.008, and SpliceAI predicts no splicing impact (max delta = 0.00, which is <0.2). The aGVGD class is C0 (not C65). Per the TP53 VCEP PP3-BP4 missense flowchart: BayesDel ≤ -0.008 + no predicted splicing differences + not C65 = BP4_Moderate. The VCEP PP3-BP4-codes spreadsheet confirms this with a pre-assigned code of BP4_moderate. Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes: c.684C>G assigned BP4_moderate. BayesDel: -0.133538 (≤ -0.008). SpliceAI max delta: 0.00 (<0.2). aGVGD Class C0.
Sources
Not met · 5 · evaluated, threshold not reached
PS3 PS3 requires evidence of a damaging functional effect. The TP53 VCEP Functional-worksheet assigns BS3 (strong benign functional evidence) for p.Asp228Glu: Kato et al. (PMID:12826609) data show the variant is Functional, and Giacomelli, Kotler, and Kawaguchi assays all report no loss of function (noLOF). The pre-assigned VCEP code is BS3, not PS3 — the variant retains wild-type-like function across all eligible assays. Details ▾Hide ▴
Evidence considered
- VCEP Functional-worksheet: D228E → BS3. Kato: Functional. Giacomelli: noLOF. Kotler: noLOF. Kawaguchi: noLOF.
Sources
PM1 PM1 requires the variant to be located in a VCEP-defined hotspot codon (175, 245, 248, 249, 273, 282) or listed in cancerhotspots.org with ≥2 somatic occurrences. p.Asp228Glu is at codon 228, which is not among the designated hotspot codons. The variant is not listed in cancerhotspots.org; the hotspot screen reports residue_significant=false and exact_variant_listed=no. Six somatic occurrences are recorded in COSMIC (COSV52662428), but this does not meet the cancerhotspots.org pathway criterion. Details ▾Hide ▴
Evidence considered
- Codon 228 not in VCEP hotspot list (175
- 245
- 248
- 249
- 273
- 282). Not listed in cancerhotspots.org. COSMIC: n=6 somatic occurrences.
PP3 PP3 for missense variants requires aGVGD Class C65 with BayesDel ≥0.16 (moderate) or Class C25-C55 with BayesDel ≥0.16 (supporting). The VCEP PP3-BP4-codes spreadsheet assigns BP4_moderate to c.684C>G (p.Asp228Glu). The BayesDel score is -0.133538 (Class C0) and SpliceAI max delta is 0.00, both falling well below PP3 thresholds. PP3 is not met; the in silico evidence supports a benign interpretation (see BP4). Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes: c.684C>G assigned BP4_moderate. BayesDel: -0.133538 (Class C0). SpliceAI max delta: 0.00. aGVGD class C0.
Sources
BA1 BA1 requires a filtering allele frequency ≥0.001 (0.1%) in any gnomAD continental subpopulation. The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. BA1 is not met. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 and v4.1
- does not meet BA1 FAF ≥0.001 threshold.
Sources
BS1 BS1 requires a filtering allele frequency ≥0.0003 (0.03%) but <0.001 in a gnomAD continental subpopulation. The variant is absent from all gnomAD datasets. BS1 is not met. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 and v4.1
- does not meet BS1 FAF ≥0.0003 threshold.
Sources
Not assessed · 8 · no assessment recorded
PS1 PS1 requires a different nucleotide change resulting in the same amino acid substitution (p.Asp228Glu) that has been classified as Pathogenic or Likely Pathogenic per TP53 VCEP specifications. Nucleotide variant c.684C>A also encodes p.Asp228Glu and is listed in the VCEP PP3-BP4-codes spreadsheet, but its VCEP clinical classification is not available in the case record. Without a VCEP P/LP comparator, PS1 cannot be assessed. Details ▾Hide ▴
Evidence considered
- c.684C>A (p.Asp228Glu) exists as a same-amino-acid comparator at the nucleotide level
- but no VCEP clinical classification is available for it.
Still missing
- Need VCEP classification for c.684C>A (p.Asp228Glu) to determine PS1 eligibility.
Sources
vcep_pp3_bp4_codes
PS2 PS2 requires tallying de novo proband points using the TP53 VCEP LFS cancer scoring table. No de novo observations or proband phenotype data are available for this variant in the case record. Details ▾Hide ▴
Still missing
- No de novo proband data available for this variant.
PS4 PS4 requires tallying proband points based on LFS-associated cancer diagnoses per the TP53 VCEP PS4-Points-Table. No proband or cohort data are available for this variant. Details ▾Hide ▴
Still missing
- No proband or case-control data available for this variant.
PM5 PM5 requires a different pathogenic or likely pathogenic missense variant at the same amino acid residue (Asp228) classified per TP53 VCEP specifications. Multiple other missense variants exist at codon 228 (e.g., D228Y, D228H, D228N, D228V, D228G, D228A), and they appear in the VCEP PP3-BP4-codes spreadsheet, but their VCEP clinical classifications (P/LP vs. VUS) are not available in the case record. Without a confirmed VCEP P/LP comparator at this residue, PM5 cannot be assessed. Details ▾Hide ▴
Evidence considered
- Multiple missense variants at codon 228 (D228Y
- D228H
- D228N
- D228V
- D228G
- D228A) exist in VCEP in silico spreadsheet
- but their VCEP clinical classifications are unknown.
Still missing
- Need VCEP clinical classification for other codon 228 missense variants to determine PM5 eligibility.
Sources
vcep_pp3_bp4_codes
PP1 PP1 requires cosegregation data (≥3 meioses for supporting, 5-6 for moderate, ≥7 for strong). No cosegregation or family data are available for this variant. Details ▾Hide ▴
Still missing
- No cosegregation or family data available for this variant.
PP4 PP4 requires observation of the variant at low variant allele fraction (VAF 5-35%) suggesting somatic mosaicism or constitutional mosaicism. No VAF data are available for this variant in the case record. Details ▾Hide ▴
Still missing
- No VAF or phenotype data available for PP4 assessment.
BS2 BS2 requires observations in unrelated cancer-free females who have reached at least 60 years of age. No such clinical observations are available for this variant. Details ▾Hide ▴
Still missing
- No data on cancer-free females ≥60 years of age carrying this variant.
BS4 BS4 requires lack of segregation in affected family members with LFS-associated cancers. No segregation data are available for this variant. Details ▾Hide ▴
Still missing
- No segregation data available.
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is restricted to null variants (nonsense, frameshift, canonical ±1,2 splice sites, initiation codon, exon deletions) per the TP53 VCEP PVS1 flowchart. NM_000546.5:c.684C>G is a missense variant (p.Asp228Glu) and does not fall into any null-variant category. Details ▾Hide ▴
Evidence considered
- Missense variant
- not a null variant. PVS1 flowchart addresses only nonsense
- frameshift
- canonical splice
- initiation codon
- and exon deletion variants.
Sources
pvs1_generic_framework ↗vcep_pvs1_flowchart
PM3 VCEPPM3 is not applicable per TP53 VCEP specifications (criteria.json: applicability = 'Not applicable'). PM3 applies to recessive disorders; TP53/Li-Fraumeni syndrome is a dominant disorder. Details ▾Hide ▴
Evidence considered
- VCEP criteria.json: PM3 applicability = Not applicable. Rule does not apply to TP53/Li-Fraumeni syndrome.
Sources
PM4 VCEPPM4 is not applicable per TP53 VCEP specifications (criteria.json: applicability = 'Not applicable'). PM4 applies to in-frame deletions/insertions and stop-loss variants; this is a missense substitution. Details ▾Hide ▴
Evidence considered
- VCEP criteria.json: PM4 applicability = Not applicable. Variant is a missense substitution
- not an in-frame indel or stop-loss.
Sources
PM6 VCEPPM6 is not applicable per TP53 VCEP specifications. The VCEP combines de novo assessment under PS2 using a points-based system; PM6 is listed as 'Not applicable' with instruction 'See above for PS2_PM6 combined rule.' Details ▾Hide ▴
Evidence considered
- VCEP criteria.json: PM6 applicability = Not applicable
- combined under PS2.
Sources
PP2 VCEPPP2 is not applicable per TP53 VCEP specifications (criteria.json: applicability = 'Not applicable'). Details ▾Hide ▴
PP5 VCEPPP5 is not applicable per TP53 VCEP specifications. The VCEP states: 'This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.' Details ▾Hide ▴
Evidence considered
- VCEP criteria.json: PP5 applicability = Not Applicable for this VCEP.
Sources
BP1 VCEPBP1 is not applicable per TP53 VCEP specifications. The VCEP states: 'This rule code does not apply to these genes, as truncating variants account for only a portion of disease causing variants.' Details ▾Hide ▴
BP2 VCEPBP2 is not applicable per TP53 VCEP specifications (criteria.json: applicability = 'Not applicable'). TP53 is a dominant disorder gene; BP2 (observed in trans with a pathogenic variant) does not apply. Details ▾Hide ▴
BP3 VCEPBP3 is not applicable per TP53 VCEP specifications (criteria.json: applicability = 'Not applicable'). BP3 applies to in-frame deletions/insertions in repetitive regions, which does not describe this substitution variant. Details ▾Hide ▴
Evidence considered
- VCEP criteria.json: BP3 applicability = Not applicable. Variant is a substitution
- not an in-frame indel in a repetitive region.
Sources
BP5 VCEPBP5 is not applicable per TP53 VCEP specifications (criteria.json: applicability = 'Not applicable'). Details ▾Hide ▴
BP6 VCEPBP6 is not applicable per TP53 VCEP specifications. The VCEP states: 'This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.' Details ▾Hide ▴
Evidence considered
- VCEP criteria.json: BP6 applicability = Not Applicable for this VCEP.
Sources
BP7 N/ABP7 applies to synonymous (silent) or intronic variants with no predicted splicing impact. NM_000546.5:c.684C>G is a missense variant (p.Asp228Glu), not a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 applies only to synonymous or intronic variants.
PS5 N/APS5 is not a criterion in the standard ACMG/AMP 2015 framework and is not defined by the TP53 VCEP specifications version 2.4.0. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- TP53
- Transcript
- NM_000546.5
- Coding (HGVS c.)
- NM_000546.5:c.684C>G
- Protein (HGVS p.)
- NP_000537.3:p.(Asp228Glu)
- GRCh38
- chr17:7674279 G>C
- GRCh37
- chr17:7577597 G>C
- ClinVar
- 926556
- COSMIC
- COSV52662428
Gene diagram
Every interpreted variant in TP53, mapped onto the exon structure of NM_000546.5. Select a row to find it on the plot.
TP53NM_000546.5
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 TP53
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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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.370
- BayesDel
- -0.134
How the predictions were used
BP4 ModerateThe variant has a BayesDel score of -0.133538, which is ≤ -0.008, and SpliceAI predicts no splicing impact (max delta = 0.00, which is <0.2). The aGVGD class is C0 (not C65). Per the TP53 VCEP PP3-BP4 missense flowchart: BayesDel ≤ -0.008 + no predicted splicing differences + not C65 = BP4_Moderate. The VCEP PP3-BP4-codes spreadsheet confirms this with a pre-assigned code of BP4_moderate. Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes: c.684C>G assigned BP4_moderate. BayesDel: -0.133538 (≤ -0.008). SpliceAI max delta: 0.00 (<0.2). aGVGD Class C0.
Sources
PP3 PP3 for missense variants requires aGVGD Class C65 with BayesDel ≥0.16 (moderate) or Class C25-C55 with BayesDel ≥0.16 (supporting). The VCEP PP3-BP4-codes spreadsheet assigns BP4_moderate to c.684C>G (p.Asp228Glu). The BayesDel score is -0.133538 (Class C0) and SpliceAI max delta is 0.00, both falling well below PP3 thresholds. PP3 is not met; the in silico evidence supports a benign interpretation (see BP4). Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes: c.684C>G assigned BP4_moderate. BayesDel: -0.133538 (Class C0). SpliceAI max delta: 0.00. aGVGD class C0.
Sources
BP7 N/ABP7 applies to synonymous (silent) or intronic variants with no predicted splicing impact. NM_000546.5:c.684C>G is a missense variant (p.Asp228Glu), not a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 applies only to synonymous or intronic variants.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.37. BayesDel score = -0.133538.
9 paper records listed. 3 cited in the classification. None of the listed paper records explicitly indicates that the variant is named.
Cited in the classification
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PMID 12826609 ↗Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.Kato S et al. · 2003 Jul 8Kato et al. performed systematic functional analysis of 2,314 p53 missense mutations using a yeast-based transactivation assay. The variant p.Asp228Glu was not identified by name in the main text; however, the VCEP Functional-worksheet (Supplementary Table S3) includes pre-assigned functional codes derived from this study's data, reporting D228E as Functional in the Kato assay.→ BS3 Does not name this variant
Source detail
Location VCEP pre-assigned code in Supplementary Table S3 (Functional-worksheet.xlsx), not in main text
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PMID 29979965 ↗A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.Kotler E et al. · 2018 Jul 5Kotler et al. created a synthetic p53 mutation library covering ~10,000 DNA-binding domain variants and measured functional impact. The variant p.Asp228Glu was not identified by name in the full text. The VCEP Functional-worksheet reports noLOF for D228E in the Kotler assay.→ BS3 Does not name this variant
Source detail
Location VCEP pre-assigned code in Supplementary Table S3 (Functional-worksheet.xlsx), not in main text
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PMID 30224644 ↗Mutational processes shape the landscape of TP53 mutations in human cancer.Giacomelli AO et al. · 2018 OctGiacomelli et al. interrogated TP53 loss-of-function screens in human cancer cell lines to characterize the mutational landscape. The variant p.Asp228Glu was not identified by name in the full text. The VCEP Functional-worksheet reports noLOF for D228E in the Giacomelli assay.→ BS3 Does not name this variant
Source detail
Location VCEP pre-assigned code in Supplementary Table S3 (Functional-worksheet.xlsx), not in main text
Other recorded publications
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PMID 11900253 ↗Rescuing the function of mutant p53.Bullock and Fersht review strategies for rescuing mutant p53 function through small molecules and peptides. The paper discusses p53 structural biology and rescue approaches at the gene level. The variant NM_000546.5:c.684C>G (p.Asp228Glu) was not identified in the full text.Does not name this variant
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PMID 8023157 ↗Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations.Cho et al. report the crystal structure of the p53 core domain bound to DNA. This structural biology paper does not discuss the specific variant NM_000546.5:c.684C>G (p.Asp228Glu).Does not name this variant
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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.Richards et al. present the ACMG/AMP standards and guidelines for sequence variant interpretation. This is a methodological guideline paper and does not discuss the specific variant NM_000546.5:c.684C>G or any individual TP53 variants.Does not name this variant
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PMID 17392385 ↗American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.Saslow D et al. · 2007Saslow et al. present American Cancer Society guidelines for breast MRI screening. This is a clinical guideline paper that mentions TP53/Li-Fraumeni syndrome in the context of high-risk screening recommendations. The variant NM_000546.5:c.684C>G was not identified in the full text.Does not name this variant
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PMID 26324357 ↗American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.Robson et al. present the ASCO policy statement update on genetic and genomic testing for cancer susceptibility. This guideline paper mentions TP53 in the context of hereditary cancer panels. The variant NM_000546.5:c.684C>G was not identified in the full text.Does not name this variant
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PMID 26140447 ↗Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents.Botkin et al. discuss ethical, legal, and psychosocial implications of genetic testing in children and adolescents. This is a background review paper and does not discuss the specific variant NM_000546.5:c.684C>G.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
5 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/135637581
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/926556/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-7577597-G-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-7674279-G-C?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-7674279-G-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000546.5%3Ac.684C…
- OncoKB ↗www.oncokb.org/gene/TP53/D228E
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=121562209
- 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
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (5 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 926556)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.37. BayesDel score = -0.133538.
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; COSV52662428, n = 6 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.