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.868C>T (p.Arg290Cys)

CA001448

216472 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 08a0ff2e-ec84-4336-94ff-fb468ba9dc88
Approved on: 2021-05-13
Published on: 2021-09-24

HGVS expressions

NM_000546.5:c.868C>T
NM_000546.5(TP53):c.868C>T (p.Arg290Cys)
NC_000017.11:g.7673752G>A
CM000679.2:g.7673752G>A
NC_000017.10:g.7577070G>A
CM000679.1:g.7577070G>A
NC_000017.9:g.7517795G>A
NG_017013.2:g.18799C>T
ENST00000269305.9:c.868C>T
ENST00000269305.8:c.868C>T
ENST00000359597.8:n.868C>T
ENST00000413465.6:n.782+429C>T
ENST00000420246.6:c.868C>T
ENST00000445888.6:c.868C>T
ENST00000455263.6:c.868C>T
ENST00000504290.5:c.472C>T
ENST00000504937.5:c.472C>T
ENST00000509690.5:c.472C>T
ENST00000510385.5:c.472C>T
ENST00000610292.4:c.751C>T
ENST00000610538.4:c.751C>T
ENST00000610623.4:c.391C>T
ENST00000615910.4:n.835C>T
ENST00000617185.4:c.868C>T
ENST00000618944.4:c.391C>T
ENST00000619186.4:c.391C>T
ENST00000619485.4:c.751C>T
ENST00000620739.4:c.751C>T
ENST00000622645.4:c.751C>T
ENST00000635293.1:c.751C>T
NM_001126112.2:c.868C>T
NM_001126113.2:c.868C>T
NM_001126114.2:c.868C>T
NM_001126115.1:c.472C>T
NM_001126116.1:c.472C>T
NM_001126117.1:c.472C>T
NM_001126118.1:c.751C>T
NM_001276695.1:c.751C>T
NM_001276696.1:c.751C>T
NM_001276697.1:c.391C>T
NM_001276698.1:c.391C>T
NM_001276699.1:c.391C>T
NM_001276760.1:c.751C>T
NM_001276761.1:c.751C>T
NM_001276695.2:c.751C>T
NM_001276696.2:c.751C>T
NM_001276697.2:c.391C>T
NM_001276698.2:c.391C>T
NM_001276699.2:c.391C>T
NM_001276760.2:c.751C>T
NM_001276761.2:c.751C>T
NM_000546.6:c.868C>T
NM_001126112.3:c.868C>T
NM_001126113.3:c.868C>T
NM_001126114.3:c.868C>T
NM_001126115.2:c.472C>T
NM_001126116.2:c.472C>T
NM_001126117.2:c.472C>T
NM_001126118.2:c.751C>T
NM_001276695.3:c.751C>T
NM_001276696.3:c.751C>T
NM_001276697.3:c.391C>T
NM_001276698.3:c.391C>T
NM_001276699.3:c.391C>T
NM_001276760.3:c.751C>T
NM_001276761.3:c.751C>T

Likely Benign

Met criteria codes 3
BS3 BP4 BS2_Supporting
Not Met criteria codes 14
BS4 BS1 PS2 PS4 PS3 PS1 BP2 BA1 PP1 PP3 PM6 PM2 PM1 PM5

Evidence Links 0

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 (PMID: 12826609) and there is no evidence of a dominant negative effect or loss of function according to Giacomelli et al. (PMID: 30224644) and Kotler et al. (PMID: 29979965) (BS3). Additionally, this variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C15 (BP4). This variant has been observed in 2-7 60+ year old females without a cancer diagnosis (BS2_Supporting; internal laboratory contributors). In summary, TP53 c.868C>T; p.Arg290Cys 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; BS2_supporting.
Met criteria codes
BS3
Kato: functional (134.2), Giacomelli: notDNE_notLOF, Kotler (notLOF, -2.04)
BP4
aGVGD = C15, BayesDel = 0.14
BS2_Supporting
4 observations in females unaffected with cancer at age 60 in Ambry internal data; 5 observations in females unaffected with cancer age 60 in Invitae internal data
Not Met criteria codes
BS4
No data available
BS1
Three alleles in different populations (one in each) in gnomad non-cancer v.2.1.1
PS2
No data available
PS4
No cases in internal data or literature that meet Revised Chompret or Classical LFS criteria
PS3
Kato: functional (134.2), Giacomelli: notDNE_notLOF, Kotler (notLOF, -2.04)
PS1
varSEAK predicts no splicing effect (Class 1)
BP2
No data available
BA1
Three alleles in different populations (one in each) in gnomad non-cancer v.2.1.1
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
aGVGD = C15, BayesDel = 0.14
PM6
No data available
PM2
Three alleles in different populations (one in each) in gnomad non-cancer v.2.1.1
PM1
Codon 290 is not in the list of hotspots. R290 not found in cancerhotspots.
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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