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 related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000546.5(TP53):c.875A>G (p.Lys292Arg)

CA16615993

406577 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 7ecc92d2-f4ef-4396-b065-463440589f86
Approved on: 2021-04-02
Published on: 2021-09-24

HGVS expressions

NM_000546.5:c.875A>G
NM_000546.5(TP53):c.875A>G (p.Lys292Arg)
NC_000017.11:g.7673745T>C
CM000679.2:g.7673745T>C
NC_000017.10:g.7577063T>C
CM000679.1:g.7577063T>C
NC_000017.9:g.7517788T>C
NG_017013.2:g.18806A>G
ENST00000503591.2:c.875A>G
ENST00000508793.6:c.875A>G
ENST00000509690.6:c.479A>G
ENST00000514944.6:c.596A>G
ENST00000604348.6:c.854A>G
ENST00000269305.9:c.875A>G
ENST00000269305.8:c.875A>G
ENST00000359597.8:c.875A>G
ENST00000413465.6:c.782+436A>G
ENST00000420246.6:c.875A>G
ENST00000445888.6:c.875A>G
ENST00000455263.6:c.875A>G
ENST00000504290.5:c.479A>G
ENST00000504937.5:c.479A>G
ENST00000509690.5:c.479A>G
ENST00000510385.5:c.479A>G
ENST00000610292.4:c.758A>G
ENST00000610538.4:c.758A>G
ENST00000610623.4:c.398A>G
ENST00000615910.4:c.842A>G
ENST00000617185.4:c.875A>G
ENST00000618944.4:c.398A>G
ENST00000619186.4:c.398A>G
ENST00000619485.4:c.758A>G
ENST00000620739.4:c.758A>G
ENST00000622645.4:c.758A>G
ENST00000635293.1:c.758A>G
NM_001126112.2:c.875A>G
NM_001126113.2:c.875A>G
NM_001126114.2:c.875A>G
NM_001126115.1:c.479A>G
NM_001126116.1:c.479A>G
NM_001126117.1:c.479A>G
NM_001126118.1:c.758A>G
NM_001276695.1:c.758A>G
NM_001276696.1:c.758A>G
NM_001276697.1:c.398A>G
NM_001276698.1:c.398A>G
NM_001276699.1:c.398A>G
NM_001276760.1:c.758A>G
NM_001276761.1:c.758A>G
NM_001276695.2:c.758A>G
NM_001276696.2:c.758A>G
NM_001276697.2:c.398A>G
NM_001276698.2:c.398A>G
NM_001276699.2:c.398A>G
NM_001276760.2:c.758A>G
NM_001276761.2:c.758A>G
NM_000546.6:c.875A>G
NM_001126112.3:c.875A>G
NM_001126113.3:c.875A>G
NM_001126114.3:c.875A>G
NM_001126115.2:c.479A>G
NM_001126116.2:c.479A>G
NM_001126117.2:c.479A>G
NM_001126118.2:c.758A>G
NM_001276695.3:c.758A>G
NM_001276696.3:c.758A>G
NM_001276697.3:c.398A>G
NM_001276698.3:c.398A>G
NM_001276699.3:c.398A>G
NM_001276760.3:c.758A>G
NM_001276761.3:c.758A>G
More

Likely Benign

Met criteria codes 2
BS3 BP4
Not Met criteria codes 8
PP3 PM1 PM5 PM2 BS2 PS1 PS3 PS4

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
Transactivation assays show retained function according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3; PMID: 12826609, 30224644). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). In summary, TP53 c.875A>G (p.Lys292Arg) meets criteria to be classified as likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3, BP4.
Met criteria codes
BS3
Kato (PMID: 12826609): functional, Giacomelli (PMID: 30224644): noDNE+noLOF, Kotler (PMID: 29979965) noLOF
functional PubMed:12826609
noDNE+noLOF PubMed:30224644
noLOF PubMed:29979965
BP4
A-GVGD: C0. BayesDel: 0.0100
Not Met criteria codes
PP3
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
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Allele Count of 1 in gnomAD v.2.1.1 (non-cancer)
BS2
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
PS4
Observed in an individual with breast cancer, age and family history not provided (PMID: 29522266)
Curation History
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