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

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

Likely Benign

• Met criteria codes: BP4 BS3

• Not Met criteria codes: PP3 PS1 PS3 PS4 PM1 PM5 PM2 BS2

Expert Panel

TP53 VCEP

Criteria Specification Information

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

• BP4: A-GVGD: C0. BayesDel: 0.0100
• BS3: Kato (PMID: 12826609): functional, Giacomelli (PMID: 30224644): noDNE+noLOF, Kotler (PMID: 29979965) noLOF

Not Met criteria codes

• PP3: 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)
• 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