About TP53
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TP53 c.610G>T, p.(Glu204Ter)
Classification
Likely pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely pathogenic classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen TP53 VCEP v2.4. 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: 0
Pathogenic criteria applied · 2
PVS1Very strong
PVS1 · very strong
NM_000546.6:c.610G>T is a nonsense variant producing a premature termination codon at p.Glu204Ter. The PTC is upstream of p.Lys351 (codon 351) and is located in exon 6, not in exon 11 or the 3'-most 50 nucleotides of exon 10, and is therefore predicted to undergo nonsense-mediated decay. Per the TP53 VCEP PVS1 flowchart (Figure 1, version 2.4), nonsense variants upstream of p.Lys351 predicted to undergo NMD are assigned PVS1 at very strong strength.
PM2Supporting
PM2 · supporting
The variant is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes), yielding an allele frequency of 0. This is below the VCEP PM2_Supporting threshold of <0.00003 (0.003%). No single genetic ancestry group has multiple alleles with frequency >0.00004.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely pathogenic
ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.4 v2.4 point-based framework: PVS1 very strong (+8) + PM2 supporting (+1) = 9 points, which maps to Likely Pathogenic.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
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.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
2 reported laboratory submissions
2 Pathogenic. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
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.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
100 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV52679869, n = 100 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, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 9 not met · 0 not assessed · 18 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000546.6:c.610G>T (p.Glu204Ter) is a nonsense variant in exon 6 of TP53, producing a premature termination codon at position 204 that is predicted to undergo nonsense-mediated decay, satisfying PVS1 at very strong strength per the TP53 VCEP PVS1 flowchart.
The variant is absent from all gnomAD population databases (v2.1, v4.1, Canada v1.0), meeting PM2 at supporting strength under the VCEP threshold of <0.00003.
The variant has been observed as a recurrent somatic mutation in COSMIC (n=100, COSV52679869) and is classified as Pathogenic by two clinical laboratories in ClinVar (ClinVarID 977783), consistent with a deleterious truncating effect.
No proband phenotype data, segregation information, de novo observations, or VAF data are available to support PS2, PS4, PP1, or PP4 scoring under the VCEP point-based system.
The VCEP functional (PS3/BS3) and in silico (PP3/BP4/BP7) criteria are limited to missense variants, in-frame deletions, synonymous variants, and intronic variants by the framework specifications and do not apply to nonsense variants. The truncating consequence is fully captured by PVS1.
Under the Tavtigian point-based classification system used by the TP53 VCEP, PVS1 (very strong = 8 points) plus PM2 (supporting = 1 point) yields a total of 9 points, which falls in the Likely Pathogenic range (6-9 points).
No criteria match.
Met · 2
PVS1 Very strongNM_000546.6:c.610G>T is a nonsense variant producing a premature termination codon at p.Glu204Ter. The PTC is upstream of p.Lys351 (codon 351) and is located in exon 6, not in exon 11 or the 3'-most 50 nucleotides of exon 10, and is therefore predicted to undergo nonsense-mediated decay. Per the TP53 VCEP PVS1 flowchart (Figure 1, version 2.4), nonsense variants upstream of p.Lys351 predicted to undergo NMD are assigned PVS1 at very strong strength. Details ▾Hide ▴
Evidence considered
- Nonsense variant p.Glu204Ter (E204*) at codon 204
- upstream of the NMD-escape boundary at p.Lys351
- PTC in exon 6 — not in exon 11 or the 3'-most 50 nt of exon 10 — predicted to trigger NMD
- TP53 VCEP PVS1 flowchart assigns PVS1 (very strong) to nonsense variants upstream of p.Lys351 with predicted NMD
- Germline loss of function is the established disease mechanism for TP53 (Li-Fraumeni syndrome
- autosomal dominant)
Sources
PM2 SupportingThe variant is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes), yielding an allele frequency of 0. This is below the VCEP PM2_Supporting threshold of <0.00003 (0.003%). No single genetic ancestry group has multiple alleles with frequency >0.00004. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: absent (AF = 0)
- gnomAD v4.1: absent (AF = 0)
- gnomAD-Canada v1.0: absent (AF = 0)
- AF = 0 < VCEP PM2_Supporting threshold of 0.00003
Sources
Not met · 9 · evaluated, threshold not reached
PS2 No de novo observation data are available for this variant. The VCEP PS2 point-based scoring system (strongly associated LFS cancers = 4 points, moderately associated = 2 points per proband) cannot be applied without proband phenotype and parental testing data. Details ▾Hide ▴
Still missing
- No proband phenotype data available for PS2 scoring
- No de novo testing results (parental genotypes unavailable)
Sources
cspec ↗vcep_table_of_lfs_cancers_and_points_for_ps2_and_pp1_code_application
PS4 The VCEP PS4 point-based scoring system requires proband-level cancer phenotype data (strongly associated LFS cancers = 4 points, moderately associated = 2 points per proband). No proband phenotype data are available in the case materials to assign PS4 points. The variant has been observed as a somatic mutation in COSMIC (n=100) and is reported as Pathogenic by two clinical laboratories in ClinVar, but these do not constitute proband-level data for VCEP PS4 scoring. Details ▾Hide ▴
PM1 The TP53 VCEP PM1 rules are explicitly limited to missense variants: (1) missense variants within codons 175, 245, 248, 249, 273, or 282 (moderate), or (2) missense variants at cancerhotspots.org with ≥10 somatic occurrences for the same amino acid change (moderate) or 2-9 occurrences (supporting). NM_000546.6:c.610G>T is a nonsense variant at codon 204, which is not among the VCEP-designated PM1 codons. The cancerhotspots.org analysis confirms this variant does not lie in a statistically significant hotspot. Details ▾Hide ▴
Evidence considered
- Codon 204 is not among the VCEP-designated PM1 codons (175
- 245
- 248
- 249
- 273
- 282)
- Variant is nonsense
- not missense — outside VCEP PM1 applicability
- Not in a statistically significant hotspot per cancerhotspots.org
Sources
PP1 No cosegregation data are available for this variant. The VCEP PP1 scoring system requires observed cosegregation in ≥3 meioses (supporting), 5-6 meioses (moderate), or ≥7 meioses (strong) across one or more families. No family studies or segregation analyses were found in the case materials. Details ▾Hide ▴
PP4 The VCEP PP4 criterion requires observation of the variant with a variant allele fraction (VAF) of 5-35% (supporting) or at least 2 independent observations with VAF 5-25% (moderate) to address potential clonal hematopoiesis/somatic mosaicism. No VAF data or phenotype information for individual probands are available in the case materials. Details ▾Hide ▴
Still missing
- No VAF data available for PP4 assessment
- No individual-level phenotype or sequencing data
Sources
BA1 The VCEP BA1 rule requires a filtering allele frequency (FAF) ≥0.001 (0.1%) in a single continental subpopulation with ≥2,000 alleles tested and ≥2 alleles present. The variant is absent from all gnomAD populations (AF = 0); it does not meet the BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: absent (AF = 0)
- gnomAD v4.1: absent (AF = 0)
- AF = 0 is far below BA1 threshold of ≥0.001
Sources
BS1 The VCEP BS1 rule requires a filtering allele frequency (FAF) ≥0.0003 (0.03%) but <0.001 in a single continental subpopulation with ≥2,000 alleles tested and ≥2 alleles present. The variant is absent from gnomAD (AF = 0); it does not meet the BS1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: absent (AF = 0)
- gnomAD v4.1: absent (AF = 0)
- AF = 0 is far below BS1 threshold of ≥0.0003
Sources
BS2 The VCEP BS2 rule requires ≥2 unrelated females who have reached at least 60 years of age without cancer (supporting), 4-7 (moderate), or ≥8 (strong), all from a single source. No such data are available in the case materials. Details ▾Hide ▴
BS4 The VCEP BS4 rule requires lack of segregation in affected family members diagnosed with LFS-associated cancers. No family segregation data are available for this variant. Details ▾Hide ▴
Not applicable · 18· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 requires a different nucleotide change producing the same amino acid alteration that has been previously classified as pathogenic per TP53 VCEP specifications. The variant c.610G>T produces a stop codon (p.Glu204Ter); no alternative nucleotide change resulting in the same nonsense codon (e.g., c.610G>A also yielding E204*) has been identified as a VCEP-classified pathogenic comparator in the case materials. Details ▾Hide ▴
Sources
PS3 N/AThe TP53 VCEP functional rules (PS3/BS3) are explicitly limited to missense variants and small in-frame deletions per the VCEP index and flowchart. The variant NM_000546.6:c.610G>T is a nonsense (stop-gain) variant and is not covered by the VCEP functional assay framework. The Functional-worksheet.xlsx (Supplementary Table S3) tabulates PS3/BS3 assignments for amino acid substitutions only and does not include nonsense entries (E204* is absent). The truncating consequence of this variant is already captured by PVS1. Details ▾Hide ▴
Evidence considered
- VCEP functional rules index states types: missense
- in-frame deletions
- Functional-worksheet.xlsx contains E204A through E204Y (missense substitutions) but not E204* (stop)
- PVS1 already accounts for the loss-of-function consequence of this truncating variant
Sources
PM3 VCEPRecessive disorder criterion for trans configuration; TP53/Li-Fraumeni syndrome is autosomal dominant. Details ▾Hide ▴
No further detail was recorded.
PM4 VCEPProtein length change due to in-frame deletion/insertion; variant is a single nucleotide substitution producing a premature stop codon. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AThe TP53 VCEP PM5 rules are explicitly limited to missense variants at an amino acid residue where a different missense variant has been previously determined to be pathogenic or likely pathogenic per VCEP specifications. NM_000546.6:c.610G>T is a nonsense variant, not a missense variant, and is therefore outside the scope of PM5 per the VCEP framework. This was confirmed by pm5_candidates.json which returned not_applicable. Details ▾Hide ▴
Evidence considered
- VCEP PM5 rules require a missense variant at the same residue
- c.610G>T is a nonsense (stop-gain) variant
- not missense
- pm5_candidates.json recommendation: not_applicable
Sources
cspec ↗pm5_candidates
PM6 VCEPThe TP53 VCEP declares PM6 Not Applicable. The VCEP applicability field for PM6 is 'Not applicable' and the criterion is not for use under this gene-specific framework. Details ▾Hide ▴
Sources
PP2 VCEPThe TP53 VCEP declares PP2 Not Applicable. The VCEP applicability field for PP2 is 'Not applicable' and the criterion is not for use under this gene-specific framework. Details ▾Hide ▴
Sources
PP3 N/AThe TP53 VCEP PP3 rules are limited to missense variants (aGVGD class + BayesDel score criteria), single amino acid in-frame deletions (BayesDel score), and exonic/intronic splice variants (SpliceAI ≥0.2). The variant c.610G>T is a nonsense (stop-gain) variant and is not covered by any VCEP PP3 rule category. The PP3-BP4-codes.xlsx (Supplementary Table S2) is explicitly a table for missense variant bioinformatic assignments and does not include nonsense entries. SpliceAI predicts no splicing impact (max delta = 0.00). Details ▾Hide ▴
Evidence considered
- VCEP PP3 flowchart targets missense
- synonymous
- intronic variants — nonsense not included
- PP3-BP4-codes.xlsx contains c.610G>C and c.610G>A (missense) but not c.610G>T (nonsense)
- SpliceAI max delta = 0.00
- no predicted splicing impact
- BayesDel score of 0.66 is available but not interpretable under VCEP PP3 rules for nonsense variants
Sources
PP5 VCEPThe TP53 VCEP declares PP5 Not Applicable. The VCEP explicitly states: 'This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.' Details ▾Hide ▴
Sources
BS3 N/AThe TP53 VCEP BS3 functional rules are explicitly limited to missense variants and small in-frame deletions per the VCEP index and functional flowchart. The variant c.610G>T is a nonsense (stop-gain) variant and is not covered by the VCEP functional assay framework. The Functional-worksheet.xlsx does not include entries for nonsense variants at this position. Details ▾Hide ▴
Evidence considered
- VCEP functional rules apply to missense variants and small in-frame deletions only
- Functional-worksheet.xlsx lists amino acid substitutions at E204 but not E204* (stop)
Sources
BP1 VCEPThe TP53 VCEP declares BP1 Not Applicable. The VCEP applicability field for BP1 is 'Not applicable' and the criterion is not for use under this gene-specific framework. Details ▾Hide ▴
Sources
BP2 VCEPThe TP53 VCEP declares BP2 Not Applicable. The VCEP applicability field for BP2 is 'Not applicable' and the criterion is not for use under this gene-specific framework. Details ▾Hide ▴
Sources
BP3 VCEPIn-frame deletion/insertion in a repetitive region without known function; variant is a single nucleotide substitution, not an in-frame indel. Details ▾Hide ▴
No further detail was recorded.
BP4 N/AThe TP53 VCEP BP4 rules are limited to missense variants (BayesDel score and aGVGD class criteria), synonymous variants, intronic variants, and single amino acid in-frame deletions. The variant c.610G>T is a nonsense (stop-gain) variant and falls outside all VCEP BP4 rule categories. SpliceAI predicts no splicing impact (max delta = 0.00). Details ▾Hide ▴
Evidence considered
- VCEP BP4 flowchart targets missense
- synonymous
- intronic variants — nonsense not included
- SpliceAI max delta = 0.00
- no predicted splicing impact
Sources
BP5 VCEPThe TP53 VCEP declares BP5 Not Applicable. The VCEP applicability field for BP5 is 'Not applicable' and the criterion is not for use under this gene-specific framework. Details ▾Hide ▴
Sources
BP6 VCEPThe TP53 VCEP declares BP6 Not Applicable. The VCEP explicitly states this criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Sources
BP7 N/AThe VCEP BP7 rules are limited to synonymous (silent) variants and intronic variants. The variant c.610G>T is a nonsense (stop-gain) substitution that changes a glutamate codon to a stop codon, and is not a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- VCEP BP7 applies to synonymous/intronic variants — c.610G>T is a nonsense variant
Sources
cspec ↗vcep_flowchart_for_application_of_pp3_2c_bp4_2c_and_bp7
PS5 N/APS5 (same nucleotide change as a previously established pathogenic variant) is not defined in the TP53 VCEP version 2.4 criteria set. The VCEP framework does not include PS5 as an applicable criterion. Details ▾Hide ▴
Sources
Identifiers
- Gene
- TP53
- Transcript
- NM_000546.6
- Coding (HGVS c.)
- NM_000546.6:c.610G>T
- Protein (HGVS p.)
- NP_000537.3:p.(Glu204Ter)
- GRCh38
- chr17:7674921 C>A
- GRCh37
- chr17:7578239 C>A
- ClinVar
- 3602771, 977783
- COSMIC
- COSV52679869
Gene diagram
Every interpreted variant in TP53, mapped onto the exon structure of NM_000546.6. Select a row to find it on the plot.
TP53NM_000546.6
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
- Not available
- BayesDel
- 0.660
How the predictions were used
PP3 N/AThe TP53 VCEP PP3 rules are limited to missense variants (aGVGD class + BayesDel score criteria), single amino acid in-frame deletions (BayesDel score), and exonic/intronic splice variants (SpliceAI ≥0.2). The variant c.610G>T is a nonsense (stop-gain) variant and is not covered by any VCEP PP3 rule category. The PP3-BP4-codes.xlsx (Supplementary Table S2) is explicitly a table for missense variant bioinformatic assignments and does not include nonsense entries. SpliceAI predicts no splicing impact (max delta = 0.00). Details ▾Hide ▴
Evidence considered
- VCEP PP3 flowchart targets missense
- synonymous
- intronic variants — nonsense not included
- PP3-BP4-codes.xlsx contains c.610G>C and c.610G>A (missense) but not c.610G>T (nonsense)
- SpliceAI max delta = 0.00
- no predicted splicing impact
- BayesDel score of 0.66 is available but not interpretable under VCEP PP3 rules for nonsense variants
Sources
BP4 N/AThe TP53 VCEP BP4 rules are limited to missense variants (BayesDel score and aGVGD class criteria), synonymous variants, intronic variants, and single amino acid in-frame deletions. The variant c.610G>T is a nonsense (stop-gain) variant and falls outside all VCEP BP4 rule categories. SpliceAI predicts no splicing impact (max delta = 0.00). Details ▾Hide ▴
Evidence considered
- VCEP BP4 flowchart targets missense
- synonymous
- intronic variants — nonsense not included
- SpliceAI max delta = 0.00
- no predicted splicing impact
Sources
BP7 N/AThe VCEP BP7 rules are limited to synonymous (silent) variants and intronic variants. The variant c.610G>T is a nonsense (stop-gain) substitution that changes a glutamate codon to a stop codon, and is not a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- VCEP BP7 applies to synonymous/intronic variants — c.610G>T is a nonsense variant
Sources
cspec ↗vcep_flowchart_for_application_of_pp3_2c_bp4_2c_and_bp7
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). BayesDel score = 0.66.
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 11753428 ↗A novel mechanism of tumorigenesis involving pH-dependent destabilization of a mutant p53 tetramer.Reports on pH-dependent destabilization of the p53-R337H mutant tetramerization domain in pediatric adrenocortical carcinoma. The specific variant NM_000546.6:c.610G>T (p.Glu204Ter) is not mentioned; the study focuses exclusively on R337H in the tetramerization domain.Does not name this variant
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PMID 11900253 ↗Rescuing the function of mutant p53.Review article on strategies to rescue mutant p53 function through small-molecule stabilization and peptide activation. Discusses TP53 mutation classes (DNA-contact, structural, denatured) and six hotspot codons (R175, G245, R248, R249, R273, R282) at the gene level. NM_000546.6:c.610G>T (p.Glu204Ter) is not mentioned in the text.Does not name this variant
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PMID 16007150 ↗The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library.Comprehensive missense mutation library analysis of p53 oligomerization domain structure-function relationships using 184 mutants. The study focuses on the C-terminal oligomerization domain (residues 323-356) and uses missense substitutions. NM_000546.6:c.610G>T (p.Glu204Ter) is outside the studied domain and is not mentioned in the abstract.Does not name this variant
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PMID 19336573 ↗High incidence of protein-truncating TP53 mutations in BRCA1-related breast cancer.Reports a high incidence of protein-truncating TP53 mutations in BRCA1-related breast cancer, sequencing TP53 exons 2-9 in 21 BRCA1-related breast tumors. The abstract notes the study identified protein-truncating TP53 mutations as a class but does not specify NM_000546.6:c.610G>T (p.Glu204Ter) individually.Does not name this variant
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PMID 21467160 ↗Prognostic significance of truncating TP53 mutations in head and neck squamous cell carcinoma.Prognostic study of TP53 mutations in 141 head and neck squamous cell carcinomas showing truncating mutations (nonsense, frameshift, splice site) as a class are associated with significantly worse overall and progression-free survival. NM_000546.6:c.610G>T (p.Glu204Ter) is not individually listed in the main text; individual mutations are in Supplementary Table S1 which was not available for review.Does not name this variant
Quoted passage
Truncating mutations are a subgroup within the disruptive mutation group and include nonsense (mutation leading to a stop codon), frameshift, and splice-site mutations. Truncating mutations lead to nonfunctional protein and thereby to a loss of function about normally functioning p53.
Results section; Supplementary Table S1 (not reviewed)
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PMID 17392385 ↗American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.Saslow D et al. · 2007American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. This is a clinical practice guideline and does not discuss any specific TP53 variants. NM_000546.6:c.610G>T (p.Glu204Ter) is not mentioned.Does not name this variant
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PMID 20301471 ↗Wilms Tumor Predisposition.Adam MP et al. · 1993GeneReviews entry on Wilms Tumor Predisposition. This resource covers WT1 and related genes; TP53 is not the focus. NM_000546.6:c.610G>T (p.Glu204Ter) is not mentioned in the abstract or available metadata.Does not name this variant
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PMID 24493721 ↗American Society of Clinical Oncology Expert Statement: collection and use of a cancer family history for oncology providers.Lu KH et al. · 2014ASCO expert statement on the collection and use of cancer family history for oncology providers. This is a clinical guidance document about family history taking practices and does not discuss any specific TP53 variants. NM_000546.6:c.610G>T (p.Glu204Ter) is not mentioned.Does not name this variant
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PMID 23619274 ↗American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders.ACMG technical standards and guidelines for microarray analysis in neoplastic disorders. This is a laboratory standards document for chromosomal microarray testing and does not discuss specific sequence variants. NM_000546.6:c.610G>T (p.Glu204Ter) is not mentioned.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
2 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/135637581
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/977783/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-7578239-C-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-7674921-C-A?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-7674921-C-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000546.6%3Ac.610G…
- OncoKB ↗www.oncokb.org/gene/TP53/E204*
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=121487587
- 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 Pathogenic (2 clinical laboratories). (ClinVarID = 977783)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). BayesDel score = 0.66.
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; COSV52679869, n = 100 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.