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.

CA000367

12365 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: ed201831-1d8d-4c6d-ad13-1055f8d3407b

HGVS expressions

NM_000546.5:c.733G>A
NC_000017.11:g.7674230C>T
CM000679.2:g.7674230C>T
NC_000017.10:g.7577548C>T
CM000679.1:g.7577548C>T
NC_000017.9:g.7518273C>T
NG_017013.2:g.18321G>A
NM_001126112.2:c.733G>A
NM_001126113.2:c.733G>A
NM_001126114.2:c.733G>A
NM_001126115.1:c.337G>A
NM_001126116.1:c.337G>A
NM_001126117.1:c.337G>A
NM_001126118.1:c.616G>A
NM_001276695.1:c.616G>A
NM_001276696.1:c.616G>A
NM_001276697.1:c.256G>A
NM_001276698.1:c.256G>A
NM_001276699.1:c.256G>A
NM_001276760.1:c.616G>A
NM_001276761.1:c.616G>A
NM_001276695.2:c.616G>A
NM_001276696.2:c.616G>A
NM_001276697.2:c.256G>A
NM_001276698.2:c.256G>A
NM_001276699.2:c.256G>A
NM_001276760.2:c.616G>A
NM_001276761.2:c.616G>A
ENST00000269305.8:c.733G>A
ENST00000359597.8:n.733G>A
ENST00000413465.6:n.733G>A
ENST00000420246.6:c.733G>A
ENST00000445888.6:c.733G>A
ENST00000455263.6:c.733G>A
ENST00000504290.5:c.337G>A
ENST00000504937.5:c.337G>A
ENST00000509690.5:c.337G>A
ENST00000510385.5:c.337G>A
ENST00000514944.5:c.454G>A
ENST00000610292.4:c.616G>A
ENST00000610538.4:c.616G>A
ENST00000610623.4:c.256G>A
ENST00000615910.4:n.700G>A
ENST00000617185.4:c.733G>A
ENST00000618944.4:c.256G>A
ENST00000619186.4:c.256G>A
ENST00000619485.4:c.616G>A
ENST00000620739.4:c.616G>A
ENST00000622645.4:c.616G>A
ENST00000635293.1:c.616G>A

Pathogenic

Met criteria codes 4
PS3 PS4 PP3 PM1
Not Met criteria codes 1
BP4

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
This variant is within a codon that is an established hotspot in the TP53 gene (PM1; PMID: 2046748). This variant has a BayesDel score > 0.16 and Align GVGD (Zebrafish) is Class 15 or higher (PP3). Transactivation assays show a low functioning allele according to Kato, et al. and there is evidence of a dominant negative effect and loss of function according to Giacomelli, et al. (PS3; PMID: 12826609, 30224644). This variant has been reported in at least 3 probands meeting Classic Li-Fraumeni syndrome criteria and at least 2 probands meeting Chompret criteria (PS4; PMID: 11370630, 24122735, 20522432, 12885464). In summary, TP53 c.733G>A; p.Gly245Ser meets criteria to be classified as pathogenic for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM1, PP3, PS3, PS4.
Met criteria codes
PS3
non-functional on T-A assay; knock in mouse available
Knock in mouse PubMed:23538418
PS4
Three probands meeting LFS criteria plus 2 probands meeting Chompret = 4 pts
PP3
AGVGD score is C65 and BayesDel score is >0.16
PM1
245 is a hotspot
Not Met criteria codes
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2019-08-28
Published on: 2020-01-24
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