TP53c.700T>ALikely pathogenic

Print report

Variant interpretation report

TP53 c.700T>A, p.(Tyr234Asn)

NM_000546.6:c.700T>A NP_000537.3:p.(Tyr234Asn) View identifiers

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.

About TP53

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 strong (pathogenic) · 2 supporting (pathogenic)
Expert rules: ClinGen TP53 VCEP v2.4.0
Other laboratories (ClinVar): 2 Pathogenic · 1 Likely pathogenic
Pipeline record: 5 Jun 2026

Evidence considered

View criteria

Applied evidence criteria

PS3 (strong): The TP53 VCEP Functional-worksheet (Supplementary Table S3) assigns PS3 at strong strength to p.Tyr234Asn. Kato et al. functional data classifies this variant as Non-functional, and the majority of other eligible assays (Giacomelli, Kotler, Funk) all demonstrate loss of function (LOF). This satisfies the VCEP PS3 rule: 'Non-functional on Kato et al. data AND loss of function (LOF) by the majority of other eligible assays.'
PM2 (supporting): This variant is absent from gnomAD v2.1 and v4.1, meeting the TP53 VCEP PM2_Supporting threshold of allele frequency <0.00003 (0.003%). The variant has zero alleles across all population databases examined, well below the PM2_Supporting cutoff.
PP3 (supporting): The TP53 VCEP PP3-BP4-codes spreadsheet (Supplementary Table S2) directly assigns PP3 to c.700T>A (p.Tyr234Asn). This variant falls in aGVGD Class C35 (C25-C55 range) with BayesDel score 0.489361 (≥0.16), meeting the VCEP PP3_Supporting rule: 'aGVGD class C25-C55 and BayesDel score ≥0.16.' SpliceAI max delta score is 0.00, confirming no confounding splice effect. REVEL score of 0.941 provides additional corroboration of deleterious prediction.

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: 3 Benign evidence criteria: 0

Pathogenic criteria applied · 3

PS3Strong

PS3 · strong

The TP53 VCEP Functional-worksheet (Supplementary Table S3) assigns PS3 at strong strength to p.Tyr234Asn. Kato et al. functional data classifies this variant as Non-functional, and the majority of other eligible assays (Giacomelli, Kotler, Funk) all demonstrate loss of function (LOF). This satisfies the VCEP PS3 rule: 'Non-functional on Kato et al. data AND loss of function (LOF) by the majority of other eligible assays.'

PM2Supporting

PM2 · supporting

This variant is absent from gnomAD v2.1 and v4.1, meeting the TP53 VCEP PM2_Supporting threshold of allele frequency <0.00003 (0.003%). The variant has zero alleles across all population databases examined, well below the PM2_Supporting cutoff.

PP3Supporting

PP3 · supporting

The TP53 VCEP PP3-BP4-codes spreadsheet (Supplementary Table S2) directly assigns PP3 to c.700T>A (p.Tyr234Asn). This variant falls in aGVGD Class C35 (C25-C55 range) with BayesDel score 0.489361 (≥0.16), meeting the VCEP PP3_Supporting rule: 'aGVGD class C25-C55 and BayesDel score ≥0.16.' SpliceAI max delta score is 0.00, confirming no confounding splice effect. REVEL score of 0.941 provides additional corroboration of deleterious prediction.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Likely pathogenic

Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v2.4.0 point-based framework: PS3 strong (+4) + PM2 supporting (+1) + PP3 supporting (+1) = 6 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.

Applied · PM2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · PP3 → SpliceAI ↗

ClinVar submissions

3 reported laboratory submissions

2 Pathogenic · 1 Likely pathogenic.

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.

Applied · PS3 → OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

35 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV52730114, n = 35 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under ClinGen TP53 VCEP v2.4.0, with the data and sources behind each one.

27 criteria with recorded statuses: 3 met · 12 not met · 0 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

Functional studies demonstrate that p.Tyr234Asn is non-functional in the Kato et al. transactivation assay with loss of function across all other eligible assays (Giacomelli, Kotler, Funk), meeting PS3 at strong strength per the TP53 VCEP v2.4.0 Functional-worksheet.

This variant is absent from gnomAD v2.1 and v4.1 population databases (allele count = 0), meeting PM2_Supporting per the TP53 VCEP threshold of allele frequency <0.003%.

Computational evidence supports a deleterious effect: aGVGD Class C35, BayesDel score 0.489, REVEL score 0.941, with no predicted splicing impact (SpliceAI max delta 0.00). The TP53 VCEP PP3-BP4-codes spreadsheet assigns PP3 at supporting level.

This variant has been reported in ClinVar as Pathogenic by two clinical laboratories and Likely pathogenic by one laboratory (ClinVar Variation ID 376692), and has been observed in somatic cancers (COSMIC, n=35).

Applying the TP53 VCEP v2.4.0 Tavtigian point system: PS3_Strong (+5) + PM2_Supporting (+1) + PP3_Supporting (+0.5) = 6.5 total points, which falls within the Likely Pathogenic range (6-9 points).

Met · 3

PS3 StrongThe TP53 VCEP Functional-worksheet (Supplementary Table S3) assigns PS3 at strong strength to p.Tyr234Asn. Kato et al. functional data classifies this variant as Non-functional, and the majority of other eligible assays (Giacomelli, Kotler, Funk) all demonstrate loss of function (LOF). This satisfies the VCEP PS3 rule: 'Non-functional on Kato et al. data AND loss of function (LOF) by the majority of other eligible assays.' Details ▾Hide ▴

Evidence considered

VCEP Functional-worksheet.xlsx: Y234N → Kato: Non-functional
Giacomelli: LOF
Kotler: LOF
Funk: LOF
Kawaguchi: NA → PS3 (strong).

Sources

vcep_functional_worksheet128266092997996530224644

PM2 SupportingThis variant is absent from gnomAD v2.1 and v4.1, meeting the TP53 VCEP PM2_Supporting threshold of allele frequency <0.00003 (0.003%). The variant has zero alleles across all population databases examined, well below the PM2_Supporting cutoff. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 (exomes)
absent from gnomAD v4.1 (exomes + genomes)
absent from gnomAD-Canada v1.0.

Sources

gnomad_v2 ↗gnomad_v4 ↗

PP3 SupportingThe TP53 VCEP PP3-BP4-codes spreadsheet (Supplementary Table S2) directly assigns PP3 to c.700T>A (p.Tyr234Asn). This variant falls in aGVGD Class C35 (C25-C55 range) with BayesDel score 0.489361 (≥0.16), meeting the VCEP PP3_Supporting rule: 'aGVGD class C25-C55 and BayesDel score ≥0.16.' SpliceAI max delta score is 0.00, confirming no confounding splice effect. REVEL score of 0.941 provides additional corroboration of deleterious prediction. Details ▾Hide ▴

Evidence considered

PP3-BP4-codes.xlsx: c.700T>A → Class C35
BayesDel 0.489361 → PP3
REVEL 0.941
SpliceAI max delta 0.00 (no splice impact).

Sources

vcep_pp3_bp4_codesrevelbayesdelspliceai ↗

Not met · 12 · evaluated, threshold not reached

PS2 No confirmed de novo occurrence identified for this variant. PS2 requires confirmed de novo origin (both maternity and paternity confirmed) in a proband with Li-Fraumeni syndrome-associated cancer. Neither ClinVar, IARC TP53, nor published literature contains a confirmed de novo report for c.700T>A (p.Tyr234Asn). Details ▾Hide ▴

Evidence considered

ClinVar submissions do not report de novo origin
exploratory search found no de novo evidence in databases or literature.

Still missing

No published family study with confirmed parental genotyping for this variant.

Sources

clinvar ↗

PS4 No case-control data or proband point tally meeting PS4 thresholds is available for this variant. PS4 requires proband counting with LFS-associated cancer points (Supporting ≥1, Moderate ≥2, Strong ≥4, Very Strong ≥8). Although this variant is recurrent in somatic cancers (COSMIC n=35), germline proband counts needed for PS4 scoring have not been compiled. Details ▾Hide ▴

Evidence considered

Variant reported in ClinVar as Pathogenic by 2 labs but without proband-level phenotype/cancer enumeration for PS4 tabulation
COSMIC reports n=35 somatic occurrences.

Still missing

No proband-level cancer phenotype data available for PS4 point tabulation.
Requires manual curation of clinical laboratory case series to enumerate LFS-cancer probands.

Sources

clinvar ↗

PM1 Codon 234 is not in the TP53 VCEP-defined major hotspot codon list (175, 245, 248, 249, 273, 282). The exact variant p.Tyr234Asn is not individually listed on cancerhotspots.org (exact_variant_listed='no'), precluding PM1_Supporting via the cancerhotspots pathway (which requires 2-9 somatic occurrences for the same amino acid change). Details ▾Hide ▴

Evidence considered

Codon 234 is not in the VCEP hotspot list
cancerhotspots.org does not list the exact Y234N variant individually.

Sources

oncokb ↗

PM5 PM5 requires a missense variant at the same amino acid residue (Y234) where a different missense change has been previously classified as pathogenic or likely pathogenic according to the TP53 VCEP specifications. While other missense variants at codon 234 (Y234C, Y234D, Y234H, Y234S) show functional PS3 evidence in the VCEP Functional-worksheet, no formal VCEP final classification (P/LP) for any codon 234 comparator variant was identified. PM5 cannot be applied without a formally classified comparator. Details ▾Hide ▴

Evidence considered

Functional-worksheet assigns PS3 to Y234C
Y234D
Y234H
Y234S but these are individual criterion codes
not formal VCEP final classifications.

Still missing

No formally VCEP-classified pathogenic comparator at residue 234.
Formal VCEP classification of other Y234 variants (Y234C
Y234D
Y234H
Y234S) would be needed to support PM5.

Sources

vcep_functional_worksheet

PP1 No cosegregation data available. PP1 requires cosegregation with LFS-associated cancers in multiple affected family members (Supporting: 3-4 meioses, Moderate: 5-6, Strong: ≥7 across >1 family). No published pedigree or family study with variant-specific cosegregation analysis was found. Details ▾Hide ▴

Evidence considered

IARC TP53 germline dataset reports 0 families with cosegregation analysis for this variant
exploratory search found no published family studies.

Still missing

No published family segregation studies for this variant.

PP4 PP4 for TP53 VCEP requires observation of the variant at low variant allele fraction (VAF 5-35%) suggesting constitutional mosaicism or clonal hematopoiesis, with specific phenotype context. No VAF data or phenotype-specific information is available for this variant from the evidence reviewed. Details ▾Hide ▴

Evidence considered

No VAF or phenotype observation data available in the evidence brief or ClinVar submissions to satisfy PP4 criteria.

Still missing

No VAF or patient phenotype data available for PP4 assessment.

BA1 The variant is absent from gnomAD v2.1 and v4.1, far below the TP53 VCEP BA1 threshold of filtering allele frequency (FAF) ≥0.001 (0.1%) in any continental subpopulation. BA1 requires the variant to be common enough in population databases to be considered a benign polymorphism. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 and v4.1
allele frequency = 0
well below the BA1 FAF ≥0.001 threshold.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 The variant is absent from gnomAD, below the TP53 VCEP BS1 threshold of FAF ≥0.0003 (0.03%) in any continental subpopulation. BS1 requires the variant to be more common than expected for a highly penetrant disorder like Li-Fraumeni syndrome. Details ▾Hide ▴

Evidence considered

Absent from gnomAD
allele frequency = 0
below the BS1 FAF ≥0.0003 threshold.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 No data on unrelated females ≥60 years of age without cancer carrying this variant. BS2 requires observation of the variant in healthy elderly females (≥8 for Strong, 4-7 for Moderate, 2-3 for Supporting) from a single source. No such observations have been reported. Details ▾Hide ▴

Evidence considered

No reported observations of this variant in cancer-free elderly females from any source.

Still missing

No data on elderly unaffected female carriers available.

BS3 BS3 is contradicted by existing functional evidence. The VCEP Functional-worksheet assigns PS3 to p.Tyr234Asn based on Non-functional status in Kato et al. data with loss of function across all other eligible assays (Giacomelli, Kotler, Funk). BS3 requires functional studies showing no damaging effect (Functional on Kato AND no LOF by majority of assays), which is the opposite of the observed evidence. Details ▾Hide ▴

Evidence considered

Functional-worksheet: Y234N → Kato: Non-functional
all eligible assays show LOF → PS3 assigned
directly contradicting BS3.

Sources

vcep_functional_worksheet128266092997996530224644

BS4 No evidence of lack of segregation in affected family members. BS4 requires observation that the variant does not segregate with LFS-associated cancers in family members. No family studies or segregation data are available for this variant. Details ▾Hide ▴

Evidence considered

No family segregation data (positive or negative) available for this variant.

Still missing

No family studies with segregation analysis for this variant.

BP4 BP4 is contradicted by computational evidence. BayesDel score is 0.489361, far above the BP4_Supporting threshold (<0.16 and >−0.008) and BP4_Moderate threshold (≤−0.008). REVEL score is 0.941. The VCEP PP3-BP4-codes spreadsheet assigns PP3 (not BP4) to this variant. SpliceAI max delta is 0.00, confirming no confounding splice impact, but the in silico predictions uniformly support a deleterious effect. Details ▾Hide ▴

Evidence considered

BayesDel 0.489361 (>> BP4 threshold)
REVEL 0.941
VCEP assigns PP3
not BP4
SpliceAI 0.00 confirms no splice artifact.

Sources

vcep_pp3_bp4_codesrevelbayesdelspliceai ↗

Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/APVS1 is not applicable to missense variants. This variant (c.700T>A, p.Tyr234Asn) is a missense substitution, not a null variant (nonsense, frameshift, canonical splice site, initiation codon, or deletion). PVS1 variant assessment confirms variant class is not in any null-variant bucket. Details ▾Hide ▴

Evidence considered

Missense substitution in exon 7
variant_bucket='other'
not a null variant eligible for PVS1.

Sources

pvs1_variant_assessmentvcep_pvs1_flowchart

PS1 N/APS1 requires a different nucleotide change producing the same amino acid change (Tyr234Asn) that has been previously classified as pathogenic by the TP53 VCEP. Tyr234Asn can only be produced by c.700T>A (TAT→AAT); no alternative nucleotide substitution yields this amino acid change. No comparator exists. Details ▾Hide ▴

Evidence considered

The p.Tyr234Asn amino acid change (TAT→AAT) is uniquely produced by c.700T>A
no other nucleotide change at codon 234 produces Asn.

PM6 VCEPPM6 is designated 'Not Applicable' by the TP53 VCEP v2.4.0. The VCEP specifies that PM6 is not for use per ClinGen SVI VCEP Review Committee recommendation. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4.0 criteria.json: PM6 applicability = 'Not applicable'.

Sources

cspec ↗

PP2 VCEPPP2 is designated 'Not Applicable' by the TP53 VCEP v2.4.0. Missense variants are a common mechanism of disease in TP53; PP2 is not used per VCEP specification. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4.0 criteria.json: PP2 applicability = 'Not applicable'.

Sources

cspec ↗

PP5 VCEPPP5 is designated 'Not Applicable for this VCEP' by the TP53 VCEP v2.4.0. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4.0 criteria.json: PP5 applicability = 'Not Applicable for this VCEP'.

Sources

cspec ↗

BP1 VCEPBP1 is designated 'Not Applicable' by the TP53 VCEP v2.4.0. This rule code does not apply to TP53, as missense variants (not just truncating variants) are a well-established cause of Li-Fraumeni syndrome. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4.0 criteria.json: BP1 applicability = 'Not applicable'
truncating variants account for only a portion of disease-causing variants.

Sources

cspec ↗

BP2 VCEPBP2 is designated 'Not Applicable' by the TP53 VCEP v2.4.0. The observation-in-trans criterion is not applicable per VCEP specification. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4.0 criteria.json: BP2 applicability = 'Not applicable'.

Sources

cspec ↗

BP3 VCEPThis is a single-nucleotide substitution (missense), not an in-frame deletion/insertion in a repetitive region. BP3 does not apply to substitution variants. Details ▾Hide ▴

Evidence considered

Substitution variant
not an in-frame indel in a repetitive region.

BP5 VCEPBP5 is designated 'Not Applicable' by the TP53 VCEP v2.4.0. This criterion (variant found in a case with an alternate molecular basis for disease) is not for use per VCEP specification. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4.0 criteria.json: BP5 applicability = 'Not applicable'.

Sources

cspec ↗

BP6 VCEPBP6 is designated 'Not Applicable for this VCEP' by the TP53 VCEP v2.4.0. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4.0 criteria.json: BP6 applicability = 'Not Applicable for this VCEP'.

Sources

cspec ↗

BP7 N/ABP7 applies to synonymous (silent) or intronic variants. This is a missense variant (c.700T>A, p.Tyr234Asn) resulting in an amino acid substitution, not a silent variant. BP7 is not applicable to missense changes. Details ▾Hide ▴

Evidence considered

Missense substitution (Tyr→Asn)
not a synonymous or intronic variant.

PS5 N/APS5 is not a recognized ACMG/AMP criterion code. The standard ACMG/AMP 2015 framework does not include a PS5 criterion. No VCEP specification defines PS5 for TP53. Details ▾Hide ▴

Evidence considered

PS5 is not defined in ACMG/AMP 2015 (PMID:25741868) or the TP53 VCEP v2.4.0 specifications.

Identifiers

Gene: TP53
Transcript: NM_000546.6
Coding (HGVS c.): NM_000546.6:c.700T>A
Protein (HGVS p.): NP_000537.3:p.(Tyr234Asn)
GRCh38: chr17:7674263 A>T
GRCh37: chr17:7577581 A>T
ClinVar: 2005578, 376692
COSMIC: COSV52730114

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 — 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 0 / 0 alleles AF 0 · 0 homozygotes · FAF 0

By genetic ancestry

gnomAD-Canada

AF 0 · 0 / 0 alleles · 0 hom

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown

-0.000

Pangolin splice gain

0.000

Other predictors

REVEL: 0.941
BayesDel: 0.489

How the predictions were used

Evidence considered

PP3-BP4-codes.xlsx: c.700T>A → Class C35
BayesDel 0.489361 → PP3
REVEL 0.941
SpliceAI max delta 0.00 (no splice impact).

Sources

vcep_pp3_bp4_codesrevelbayesdelspliceai ↗

Evidence considered

BayesDel 0.489361 (>> BP4 threshold)
REVEL 0.941
VCEP assigns PP3
not BP4
SpliceAI 0.00 confirms no splice artifact.

Sources

vcep_pp3_bp4_codesrevelbayesdelspliceai ↗

Evidence considered

Missense substitution (Tyr→Asn)
not a synonymous or intronic variant.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.941. BayesDel score = 0.489361.

6 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

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Kato S et al. · 2003

No paper-specific finding is recorded.

PMID 12826609 ↗
A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

Kotler E et al. · 2018

No paper-specific finding is recorded.

PMID 29979965 ↗
Mutational processes shape the landscape of TP53 mutations in human cancer.

Giacomelli AO et al. · 2018

No paper-specific finding is recorded.

PMID 30224644 ↗
TP53 Variations in Human Cancers: New Lessons from the IARC TP53 Database and Genomics Data.

No paper-specific finding is recorded.

PMID 27328919 ↗
p53 gene mutations in osteosarcomas of low-grade malignancy.

No paper-specific finding is recorded.

PMID 9824113 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

No paper-specific finding is recorded.

PMID 28492532 ↗

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 · 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

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.

ClinVar

This variant has been reported in ClinVar as Pathogenic (2 clinical laboratories) and as Likely pathogenic (1 clinical laboratory). (ClinVarID = 376692)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.941. BayesDel score = 0.489361.

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 lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52730114, n = 35 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.