Evidence Repository - Clinical Genome Resources

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

Variant: NM_000546.5(TP53):c.760A>G (p.Ile254Val)

CA001720

406605 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: fca61001-1f1b-4755-907b-f96fc6002915

Approved on: 2021-08-03

Published on: 2021-09-24

HGVS expressions

NM_000546.5:c.760A>G

NM_000546.5(TP53):c.760A>G (p.Ile254Val)

ENST00000269305.9:c.760A>G

ENST00000269305.8:c.760A>G

ENST00000359597.8:n.760A>G

ENST00000413465.6:n.760A>G

ENST00000420246.6:c.760A>G

ENST00000445888.6:c.760A>G

ENST00000455263.6:c.760A>G

ENST00000504290.5:c.364A>G

ENST00000504937.5:c.364A>G

ENST00000509690.5:c.364A>G

ENST00000510385.5:c.364A>G

ENST00000610292.4:c.643A>G

ENST00000610538.4:c.643A>G

ENST00000610623.4:c.283A>G

ENST00000615910.4:n.727A>G

ENST00000617185.4:c.760A>G

ENST00000618944.4:c.283A>G

ENST00000619186.4:c.283A>G

ENST00000619485.4:c.643A>G

ENST00000620739.4:c.643A>G

ENST00000622645.4:c.643A>G

ENST00000635293.1:c.643A>G

NM_001126112.2:c.760A>G

NM_001126113.2:c.760A>G

NM_001126114.2:c.760A>G

NM_001126115.1:c.364A>G

NM_001126116.1:c.364A>G

NM_001126117.1:c.364A>G

NM_001126118.1:c.643A>G

NM_001276695.1:c.643A>G

NM_001276696.1:c.643A>G

NM_001276697.1:c.283A>G

NM_001276698.1:c.283A>G

NM_001276699.1:c.283A>G

NM_001276760.1:c.643A>G

NM_001276761.1:c.643A>G

NM_001276695.2:c.643A>G

NM_001276696.2:c.643A>G

NM_001276697.2:c.283A>G

NM_001276698.2:c.283A>G

NM_001276699.2:c.283A>G

NM_001276760.2:c.643A>G

NM_001276761.2:c.643A>G

NM_000546.6:c.760A>G

NM_001126112.3:c.760A>G

NM_001126113.3:c.760A>G

NM_001126114.3:c.760A>G

NM_001126115.2:c.364A>G

NM_001126116.2:c.364A>G

NM_001126117.2:c.364A>G

NM_001126118.2:c.643A>G

NM_001276695.3:c.643A>G

NM_001276696.3:c.643A>G

NM_001276697.3:c.283A>G

NM_001276698.3:c.283A>G

NM_001276699.3:c.283A>G

NM_001276760.3:c.643A>G

NM_001276761.3:c.643A>G

NC_000017.11:g.7674203T>C

CM000679.2:g.7674203T>C

NC_000017.10:g.7577521T>C

CM000679.1:g.7577521T>C

NC_000017.9:g.7518246T>C

NG_017013.2:g.18348A>G

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"

BS3 PP3 BS2_Supporting

BS4 BS1 BP2 BP4 PS2 PS4 PS3 PS1 BA1 PP1 PM6 PM2 PM1 PM5

Evidence Links 0

Expert Panel

TP53 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

TP53 VCEP

This variant has a BayesDel score > 0.16 and Align GVGD (Zebrafish) is Class 15 or higher (PP3). 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 been observed in 7 60+ year old females without a cancer diagnosis (BS2_Supporting; Internal laboratory contributor). In summary, TP53 c.760A>G (p.Ile254Val) 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: PP3, BS3, BS2_Supporting.

BS3

Kato functional, Giacomelli noLOF/noDNE, Kotler noLOF

PP3

BayesDel 0.17079, AlignGVGD C25

BS2_Supporting

2 Europeans in FLOSSIES, 4 cancer-free females >60 years of age in Ambry internal data; 7 cancer-free females >60 years of age in Invitae internal data

BS4