Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000546.5(TP53):c.892G>T (p.Glu298Ter)

CA000484

93323 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 42caf4f2-7ef5-45d4-a593-271e92b9ca88
Approved on: 2024-08-05
Published on: 2024-08-05

HGVS expressions

NM_000546.5:c.892G>T
NM_000546.5(TP53):c.892G>T (p.Glu298Ter)
NC_000017.11:g.7673728C>A
CM000679.2:g.7673728C>A
NC_000017.10:g.7577046C>A
CM000679.1:g.7577046C>A
NC_000017.9:g.7517771C>A
NG_017013.2:g.18823G>T
ENST00000503591.2:c.892G>T
ENST00000508793.6:c.892G>T
ENST00000509690.6:c.496G>T
ENST00000514944.6:c.613G>T
ENST00000604348.6:c.871G>T
ENST00000269305.9:c.892G>T
ENST00000269305.8:c.892G>T
ENST00000359597.8:c.892G>T
ENST00000413465.6:c.782+453G>T
ENST00000420246.6:c.892G>T
ENST00000445888.6:c.892G>T
ENST00000455263.6:c.892G>T
ENST00000504290.5:c.496G>T
ENST00000504937.5:c.496G>T
ENST00000509690.5:c.496G>T
ENST00000510385.5:c.496G>T
ENST00000610292.4:c.775G>T
ENST00000610538.4:c.775G>T
ENST00000610623.4:c.415G>T
ENST00000615910.4:c.859G>T
ENST00000617185.4:c.892G>T
ENST00000618944.4:c.415G>T
ENST00000619186.4:c.415G>T
ENST00000619485.4:c.775G>T
ENST00000620739.4:c.775G>T
ENST00000622645.4:c.775G>T
ENST00000635293.1:c.775G>T
NM_001126112.2:c.892G>T
NM_001126113.2:c.892G>T
NM_001126114.2:c.892G>T
NM_001126115.1:c.496G>T
NM_001126116.1:c.496G>T
NM_001126117.1:c.496G>T
NM_001126118.1:c.775G>T
NM_001276695.1:c.775G>T
NM_001276696.1:c.775G>T
NM_001276697.1:c.415G>T
NM_001276698.1:c.415G>T
NM_001276699.1:c.415G>T
NM_001276760.1:c.775G>T
NM_001276761.1:c.775G>T
NM_001276695.2:c.775G>T
NM_001276696.2:c.775G>T
NM_001276697.2:c.415G>T
NM_001276698.2:c.415G>T
NM_001276699.2:c.415G>T
NM_001276760.2:c.775G>T
NM_001276761.2:c.775G>T
NM_000546.6:c.892G>T
NM_001126112.3:c.892G>T
NM_001126113.3:c.892G>T
NM_001126114.3:c.892G>T
NM_001126115.2:c.496G>T
NM_001126116.2:c.496G>T
NM_001126117.2:c.496G>T
NM_001126118.2:c.775G>T
NM_001276695.3:c.775G>T
NM_001276696.3:c.775G>T
NM_001276697.3:c.415G>T
NM_001276698.3:c.415G>T
NM_001276699.3:c.415G>T
NM_001276760.3:c.775G>T
NM_001276761.3:c.775G>T
More

Pathogenic

Met criteria codes 4
PP4 PS4_Supporting PVS1 PM2_Supporting
Not Met criteria codes 14
BP7 BP4 PS1 PS3 PS2 PP3 PP1 PM5 PM1 BA1 BS2 BS4 BS3 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
The NM_000546.6 c.892G>T (p.Glu298Ter) is a TP53 nonsense variant inducing a premature termination codon upstream of p.Lys351. The variant is predicted to undergo nonsense-mediated decay (PVS1). This variant has been observed in 1 family meeting Revised Chompret criteria. This proband was under the age of 40 diagnosed with a HER2+ breast cancer. Based on this evidence, this variant scores 1 total point meeting the TP53 VCEP phenotype scoring criteria of 1-1.5 points. (PS4_Supporting; Internal lab contributors: SCV000278127.7). At least one individual with this variant was found to have a variant allele fraction 25-35%, which is a significant predictor of variant pathogenicity (PP4, PMID: 34906512, SCV000278127.7). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for Li Fraumeni Syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: PVS1, PS4_Supporting, PP4, PM2_Supporting. (Bayesian Points: 11; VCEP specifications version 2.0; 7/24/2024)
Met criteria codes
PP4
At least one individual with this variant was found to have a variant allele fraction 25-35%, which is a significant predictor of variant pathogenicity (PP4, PMID: 34906512, SCV000278127.7).
PS4_Supporting
This variant has been observed in 1 family meeting Revised Chompret criteria. This proband was under the age of 40 diagnosed with a HER2+ breast cancer. Based on this evidence, this variant scores 1 total point meeting the TP53 VCEP phenotype scoring criteria of 1-1.5 points. (PS4_Supporting; Internal lab contributors: SCV000278127.7).
PVS1
The NM_000546.6 c.892C>T (p.Glu298Ter) is a TP53 nonsense varianti upstream of p.Lys351. The variant is predicted to undergo nonsense-mediated decay (PVS1).
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
Not Met criteria codes
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.