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]
Link to SEPIO compliant JSON-LD document
  • 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
ENST00000269305.9:c.875A>G
ENST00000269305.8:c.875A>G
ENST00000359597.8:n.875A>G
ENST00000413465.6:n.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:n.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

Likely Benign

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

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
noLOF PubMed:29979965
functional PubMed:12826609
noDNE+noLOF PubMed:30224644
BP4
A-GVGD: C0. BayesDel: 0.0100
Not Met criteria codes
BS2
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)
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
PP3
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)
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
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