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TP53c.214C>TUncertain significance
Print report
Variant interpretation report

TP53 c.214C>T, p.(Pro72Ser)

NM_000546.5:c.214C>T NP_000537.3:p.(Pro72Ser) View identifiers
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.

About TP53

No gene-level summary was recorded for this case.

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: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting

The variant is present at very low frequency in population databases. In gnomAD v2.1, the total allele frequency is 0.00160% (4/250,672 alleles), below the VCEP PM2_Supporting threshold of 0.003%. The highest subpopulation frequency (European non-Finnish) is 0.00353% (4/113,442 alleles), below the VCEP subpopulation cutoff of 0.004%. In gnomAD v4.1, the total allele frequency is 0.00068% (11/1,613,668 alleles). The variant is absent from gnomAD-Canada v1.0.

Benign criteria applied · 1
BP4Moderate
BP4 · moderate

The TP53 VCEP PP3-BP4-codes spreadsheet (Supplementary Table S2) directly assigns BP4_moderate to c.214C>T (p.Pro72Ser). The variant has a BayesDel score of -0.202922 (Class C0), which is ≤ -0.008, meeting the VCEP BP4_Moderate threshold. aGVGD class is C0 (not C65, so no exclusion applies). SpliceAI predicts no splicing impact (max delta = 0.00, which is < 0.2), satisfying the requirement of no predicted splicing differences.

Recorded classification: Uncertain significance

Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v2.4.0 point-based framework: PM2 supporting (+1) + BP4 moderate (-2) = -1 points, 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
11 / 1,613,668 alleles

gnomAD v4.1: 11 / 1,613,668 alleles. Recorded AF 6.81677e-06. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 1.59571e-05; MAF= 0.00160%, 4/250672 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.52603e-05; MAF= 0.00353%, 4/113442 alleles, homozygotes = 0); grpmax FAF= 1.124e-05.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

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 · BP4 → SpliceAI ↗
ClinVar submissions
2 reported laboratory submissions

1 Likely benign · 1 Uncertain significance.

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. TP53, a tumor suppressor in the DNA damage pathway, is the most frequently mutated gene in cancer.

No listed criterion applied OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
6 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV52665238, n = 6 times).

Cancer Hotspots

This variant does not lie 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.

26 criteria with recorded statuses: 2 met · 10 not met · 3 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_000546.5:c.214C>T (p.Pro72Ser) is a missense variant in exon 4 of TP53 at codon 72, a known common polymorphic site (rs1042522).

The variant is present at very low frequency in gnomAD v2.1 (4/250,672 alleles; AF=0.00160%) and v4.1 (11/1,613,668 alleles; AF=0.00068%), meeting the TP53 VCEP PM2_Supporting threshold of <0.003% total allele frequency with subpopulation AF <0.004%.

The variant is assigned BP4_moderate by the TP53 VCEP bioinformatic codes (Supplementary Table S2), with a BayesDel score of -0.202922 and no predicted splicing impact (SpliceAI max delta = 0.00).

The variant has been reported in ClinVar as Likely benign (Ambry Genetics, 1 submission) and Uncertain significance (Labcorp/Invitae, 1 submission). No expert panel review is available. (ClinVar VariationID: 485023)

The variant has been observed in somatic cancers (COSMIC, COSV52665238, n=6), but lies outside the TP53 VCEP-defined mutational hotspots (codons 175, 245, 248, 249, 273, 282).

No functional data from VCEP-eligible assays are available for p.Pro72Ser; the variant is absent from the VCEP Functional-worksheet (Supplementary Table S3).

Under the Tavtigian point-based system (TP53 VCEP v2.4.0), the evidence tally is PM2_Supporting (+1) + BP4_Moderate (-2) = -1 point, consistent with a classification of Uncertain Significance.

The VCEP CAVEAT allowing reclassification of -1 points to Likely Benign (requiring ≥2 benign codes and PM2_Supporting as the only pathogenic code) is not met, as only one benign code (BP4_Moderate) is applied.

Met · 2

PM2 SupportingThe variant is present at very low frequency in population databases. In gnomAD v2.1, the total allele frequency is 0.00160% (4/250,672 alleles), below the VCEP PM2_Supporting threshold of 0.003%. The highest subpopulation frequency (European non-Finnish) is 0.00353% (4/113,442 alleles), below the VCEP subpopulation cutoff of 0.004%. In gnomAD v4.1, the total allele frequency is 0.00068% (11/1,613,668 alleles). The variant is absent from gnomAD-Canada v1.0. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 total AF=0.00160% (<0.003% PM2_Supporting threshold)
  • gnomAD v2.1 grpmax FAF=1.12e-05 (NFE subpopulation AF=0.00353% < 0.004%)
  • gnomAD v4.1 total AF=0.00068%
  • Absent from gnomAD-Canada v1.0
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
BP4 ModerateThe TP53 VCEP PP3-BP4-codes spreadsheet (Supplementary Table S2) directly assigns BP4_moderate to c.214C>T (p.Pro72Ser). The variant has a BayesDel score of -0.202922 (Class C0), which is ≤ -0.008, meeting the VCEP BP4_Moderate threshold. aGVGD class is C0 (not C65, so no exclusion applies). SpliceAI predicts no splicing impact (max delta = 0.00, which is < 0.2), satisfying the requirement of no predicted splicing differences. Details ▾Hide ▴
Evidence considered
  • VCEP PP3-BP4-codes.xlsx directly assigns BP4_moderate to c.214C>T
  • BayesDel -0.202922 ≤ -0.008 (meets BP4_Moderate threshold)
  • aGVGD Class C0 (not C65
  • no exclusion)
  • SpliceAI max delta = 0.00 < 0.2 (no predicted splicing impact)
Sources
vcep_pp3_bp4_codesbayesdelspliceai ↗

Not met · 10 · evaluated, threshold not reached

PS2 No de novo observation data are available for this variant. No proband-specific information with confirmed parentage or LFS-associated cancer phenotype was provided in the case materials. Details ▾Hide ▴
Still missing
  • No de novo observation data available.
PM1 Codon 72 is not among the TP53 VCEP-defined mutational hotspots (codons 175, 245, 248, 249, 273, 282). The variant is not listed at cancerhotspots.org as a significant residue, and the exact variant is not listed as a recurrent hotspot. Details ▾Hide ▴
Evidence considered
  • Codon 72 not in VCEP hotspot list
  • cancerhotspots.org residue_significant=false
  • exact_variant_listed=no.
PM5 Codon 72 is a known common polymorphic site (rs1042522, Pro72Arg). No other missense variants at this codon have been classified as pathogenic or likely pathogenic under the TP53 VCEP specifications. The PM5 candidate search identified zero eligible comparator variants at this residue. Details ▾Hide ▴
Evidence considered
  • Zero same-residue pathogenic/likely pathogenic comparator variants per VCEP classification
  • codon 72 is a known benign polymorphic site.
Sources
pm5_candidates
PP1 No cosegregation data are available for this variant. PP1 under TP53 VCEP requires specific meioses counts (3-4 meioses for Supporting, 5-6 for Moderate, ≥7 for Strong) in families with LFS-associated cancers. Details ▾Hide ▴
Still missing
  • No cosegregation data available.
PP3 The TP53 VCEP PP3-BP4-codes spreadsheet (Supplementary Table S2) directly assigns BP4_moderate to c.214C>T, not PP3. The BayesDel score is -0.202922 (Class C0), which does not meet the PP3 thresholds (BayesDel ≥ 0.16 required for PP3_Supporting or PP3_Moderate). REVEL score is 0.314, but the VCEP uses BayesDel and aGVGD, not REVEL, for PP3/BP4 adjudication. Details ▾Hide ▴
Evidence considered
  • VCEP PP3-BP4-codes.xlsx assigns BP4_moderate (not PP3) to c.214C>T
  • BayesDel -0.202922 < 0.16 threshold for PP3
  • aGVGD Class C0
Sources
vcep_pp3_bp4_codesbayesdel
PP4 PP4 under the TP53 VCEP is based on variant allele fraction (VAF) observations in blood specimens (5-25% for Moderate, 5-35% for Supporting), reflecting concern for clonal hematopoiesis/somatic mosaicism. No VAF data are provided for this variant to meet PP4 thresholds. Details ▾Hide ▴
Still missing
  • No VAF data available for PP4 adjudication.
BA1 The highest filtering allele frequency (FAF) observed in any gnomAD continental subpopulation is 1.12e-05 (gnomAD v2.1, European non-Finnish). This is far below the VCEP BA1 threshold of ≥ 0.001 (0.1%). Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 grpmax FAF=1.12e-05 ≪ 0.001 BA1 threshold
  • gnomAD v4.1 grpmax FAF=4.29e-06 ≪ 0.001.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 The highest filtering allele frequency in any gnomAD continental subpopulation is 1.12e-05 (v2.1 grpmax FAF), which falls below the VCEP BS1 threshold of ≥ 0.0003 (0.03%). The subpopulation with the highest frequency, European non-Finnish (AF=0.00353%, 4/113,442), also remains below this threshold. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 grpmax FAF=1.12e-05 < 0.0003 BS1 threshold
  • NFE subpopulation AF=0.00353% ≪ 0.03%.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS2 No data are available regarding observation of this variant in unrelated females who have reached at least 60 years of age without cancer, as required for BS2 under the TP53 VCEP. Details ▾Hide ▴
Still missing
  • No healthy elderly female observation data available.
BS4 No segregation data are available to assess lack of segregation with LFS-associated cancers in affected family members, as required for BS4 under the TP53 VCEP. Details ▾Hide ▴
Still missing
  • No segregation or family data available.

Not assessed · 3 · no assessment recorded

PS3 The TP53 VCEP Functional-worksheet (Supplementary Table S3) does not contain an entry for the p.Pro72Ser (P72S) amino acid substitution. Codon 72 is a known common polymorphic site (rs1042522, Pro72Arg). No functional data from VCEP-eligible assays (Kato, Funk, Giacomelli, Kotler, Kawaguchi) are available for this specific variant. Details ▾Hide ▴
Evidence considered
  • P72S absent from VCEP Functional-worksheet.xlsx
  • no eligible functional assay data available.
Still missing
  • No functional data from VCEP-eligible assays for p.Pro72Ser.
PS4 No proband-level phenotype data or LFS cancer point tallies are available in the case materials. PS4 under the TP53 VCEP requires proband-specific cancer diagnoses scored against the Li-Fraumeni syndrome points table (strongly associated cancers = 4 points, moderately associated = 2 points). Details ▾Hide ▴
Still missing
  • No proband-level clinical phenotype or cancer history data available for PS4 scoring.
BS3 The TP53 VCEP Functional-worksheet (Supplementary Table S3) does not contain an entry for the p.Pro72Ser (P72S) amino acid substitution. No functional data from VCEP-eligible assays (Kato, Funk, Giacomelli, Kotler, Kawaguchi) are available for this variant. BS3 cannot be applied without assay data. Details ▾Hide ▴
Evidence considered
  • P72S absent from VCEP Functional-worksheet.xlsx
  • no eligible functional data.
Still missing
  • No functional data from VCEP-eligible assays for p.Pro72Ser.
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000546.5:c.214C>T is a missense variant (p.Pro72Ser), not a null variant. PVS1 under the TP53 VCEP is applicable only to nonsense, frameshift, canonical splice site, initiation codon, and CNV variants as defined in the PVS1 flowchart. Details ▾Hide ▴
Evidence considered
  • Missense variant
  • not eligible for PVS1 adjudication per TP53 VCEP PVS1 decision tree.
PS1 N/Ap.Pro72Ser is produced by c.214C>T (CCC→TCC). No alternative single-nucleotide change at codon 72 produces the same amino acid change (Ser). PS1 requires the same amino acid change from a different nucleotide change, which is not possible for this variant. Details ▾Hide ▴
Evidence considered
  • Only one nucleotide path (C>T) yields Ser from the Pro72 codon (CCC)
  • no alternate nucleotide change exists.
PM6 VCEPPM6 is not applicable under the TP53 VCEP specifications (version 2.4.0). Details ▾Hide ▴
Evidence considered
  • Not applicable per VCEP.
PP2 VCEPPP2 is not applicable under the TP53 VCEP specifications. Details ▾Hide ▴
Evidence considered
  • Not applicable per VCEP.
PP5 VCEPPP5 is not recommended for use by the ClinGen Sequence Variant Interpretation VCEP Review Committee for TP53. Details ▾Hide ▴
Evidence considered
  • Not applicable per VCEP.
BP1 VCEPBP1 is not applicable under the TP53 VCEP; truncating variants account for only a portion of disease-causing variants in TP53. Details ▾Hide ▴
Evidence considered
  • Not applicable per VCEP.
BP2 VCEPBP2 is not applicable under the TP53 VCEP specifications for this variant. Details ▾Hide ▴
Evidence considered
  • Not applicable per VCEP.
BP5 VCEPBP5 is not applicable under the TP53 VCEP specifications. Details ▾Hide ▴
Evidence considered
  • Not applicable per VCEP.
BP6 VCEPBP6 is not recommended for use by the ClinGen Sequence Variant Interpretation VCEP Review Committee for TP53. Details ▾Hide ▴
Evidence considered
  • Not applicable per VCEP.
BP7 N/Ac.214C>T is a missense variant (p.Pro72Ser), not a synonymous (silent) or intronic variant. BP7 under the TP53 VCEP applies only to synonymous variants or intronic variants outside ±1,2 positions. Details ▾Hide ▴
Evidence considered
  • Missense variant
  • not eligible for BP7 which is limited to synonymous/intronic variants per VCEP.
PS5 N/ASkipped per adjudication instructions. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene
TP53
Transcript
NM_000546.5
Coding (HGVS c.)
NM_000546.5:c.214C>T
Protein (HGVS p.)
NP_000537.3:p.(Pro72Ser)
GRCh38
chr17:7676155 G>A
GRCh37
chr17:7579473 G>A
ClinVar
704964, 485023
COSMIC
COSV52665238

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…
gnomAD v4.1 11 / 1,613,668 alleles AF 6.82e-06 · 0 homozygotes · FAF 4.29e-06
gnomAD v2.1 4 / 250,672 alleles AF 1.6e-05 · 0 homozygotes · FAF 1.12e-05
gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 6.8e-06 · 11 / 1,613,668 alleles · 0 hom · FAF 4.3e-06
African/African American1 / 74,888 1.3e-05
European (non-Finnish)10 / 1,179,974 8.5e-06
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.

gnomAD v2.1

AF 1.6e-05 · 4 / 250,672 alleles · 0 hom · FAF 1.1e-05
European (non-Finnish)4 / 113,442 3.5e-05
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 6.81677e-06; MAF= 0.00068%, 11/1613668 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 1.33533e-05; MAF= 0.00134%, 1/74888 alleles, homozygotes = 0); grpmax FAF= 4.29e-06.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 1.59571e-05; MAF= 0.00160%, 4/250672 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.52603e-05; MAF= 0.00353%, 4/113442 alleles, homozygotes = 0); grpmax FAF= 1.124e-05.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown
-0.020
Pangolin splice gain
0.010

Other predictors

REVEL
0.314
BayesDel
-0.203

How the predictions were used

BP4 ModerateThe TP53 VCEP PP3-BP4-codes spreadsheet (Supplementary Table S2) directly assigns BP4_moderate to c.214C>T (p.Pro72Ser). The variant has a BayesDel score of -0.202922 (Class C0), which is ≤ -0.008, meeting the VCEP BP4_Moderate threshold. aGVGD class is C0 (not C65, so no exclusion applies). SpliceAI predicts no splicing impact (max delta = 0.00, which is < 0.2), satisfying the requirement of no predicted splicing differences. Details ▾Hide ▴
Evidence considered
  • VCEP PP3-BP4-codes.xlsx directly assigns BP4_moderate to c.214C>T
  • BayesDel -0.202922 ≤ -0.008 (meets BP4_Moderate threshold)
  • aGVGD Class C0 (not C65
  • no exclusion)
  • SpliceAI max delta = 0.00 < 0.2 (no predicted splicing impact)
Sources
vcep_pp3_bp4_codesbayesdelspliceai ↗
PP3 The TP53 VCEP PP3-BP4-codes spreadsheet (Supplementary Table S2) directly assigns BP4_moderate to c.214C>T, not PP3. The BayesDel score is -0.202922 (Class C0), which does not meet the PP3 thresholds (BayesDel ≥ 0.16 required for PP3_Supporting or PP3_Moderate). REVEL score is 0.314, but the VCEP uses BayesDel and aGVGD, not REVEL, for PP3/BP4 adjudication. Details ▾Hide ▴
Evidence considered
  • VCEP PP3-BP4-codes.xlsx assigns BP4_moderate (not PP3) to c.214C>T
  • BayesDel -0.202922 < 0.16 threshold for PP3
  • aGVGD Class C0
Sources
vcep_pp3_bp4_codesbayesdel
BP7 N/Ac.214C>T is a missense variant (p.Pro72Ser), not a synonymous (silent) or intronic variant. BP7 under the TP53 VCEP applies only to synonymous variants or intronic variants outside ±1,2 positions. Details ▾Hide ▴
Evidence considered
  • Missense variant
  • not eligible for BP7 which is limited to synonymous/intronic variants per VCEP.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.314. BayesDel score = -0.202922.

5 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

  • Li-Fraumeni Syndrome.
    Adam MP et al. · 1993
    GeneReviews chapter on Li-Fraumeni Syndrome providing clinical characteristics, diagnosis, and management recommendations. No mention of NM_000546.5:c.214C>T (p.Pro72Ser) or any specific TP53 variant.
    Does not name this variant
    PMID 20301488 ↗
  • American Society of Clinical Oncology Expert Statement: collection and use of a cancer family history for oncology providers.
    Lu KH et al. · 2014
    American Society of Clinical Oncology (ASCO) expert statement on collection and use of cancer family history for oncology providers. Provides recommendations for family history documentation but does not discuss specific TP53 variants or mention c.214C>T (p.Pro72Ser).
    Does not name this variant
    PMID 24493721 ↗
  • A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.
    Hampel H et al. · 2015
    ACMG/NSGC practice guideline on referral indications for cancer predisposition assessment. Lists criteria for referral to cancer genetics consultation by tumor type and syndrome (including Li-Fraumeni syndrome). No specific TP53 variants are discussed.
    Does not name this variant
    PMID 25394175 ↗
  • Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version.
    PDQ Cancer Genetics Editorial Board · 2002
    PDQ cancer genetics summary on the genetics of breast and gynecologic cancers. Provides gene-level overview of hereditary cancer syndromes including TP53/Li-Fraumeni syndrome. No specific variant data for c.214C>T (p.Pro72Ser).
    Does not name this variant
    PMID 26389210 ↗
  • Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version.
    PDQ Cancer Genetics Editorial Board · 2002
    PDQ summary on cancer genetics risk assessment and counseling. Discusses general principles of cancer genetic risk assessment. No mention of NM_000546.5:c.214C>T (p.Pro72Ser).
    Does not name this variant
    PMID 26389258 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 11 / 1,613,668 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 1 Likely benign · 1 Uncertain significance 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

This variant is present in gnomAD v4.1 (AF= 6.81677e-06; MAF= 0.00068%, 11/1613668 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 1.33533e-05; MAF= 0.00134%, 1/74888 alleles, homozygotes = 0); grpmax FAF= 4.29e-06.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 1.59571e-05; MAF= 0.00160%, 4/250672 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.52603e-05; MAF= 0.00353%, 4/113442 alleles, homozygotes = 0); grpmax FAF= 1.124e-05.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely benign (1 clinical laboratory) and as Uncertain significance (1 clinical laboratory). (ClinVarID = 485023)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.314. BayesDel score = -0.202922.

Functional

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. TP53, a tumor suppressor in the DNA damage pathway, is the most frequently mutated gene in cancer.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52665238, n = 6 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.