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.105G>C (p.Leu35Phe)

CA000024

142562 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 9f61138a-40be-4434-b6e0-cba991e23049

HGVS expressions

NM_000546.5:c.105G>C
NM_000546.5(TP53):c.105G>C (p.Leu35Phe)
ENST00000269305.9:c.105G>C
ENST00000269305.8:c.105G>C
ENST00000359597.8:n.105G>C
ENST00000413465.6:n.105G>C
ENST00000420246.6:c.105G>C
ENST00000445888.6:c.105G>C
ENST00000455263.6:c.105G>C
ENST00000503591.1:c.105G>C
ENST00000505014.5:n.361G>C
ENST00000508793.5:c.105G>C
ENST00000509690.5:c.-21-1028G>C
ENST00000514944.5:c.96+118G>C
ENST00000604348.5:c.105G>C
ENST00000610292.4:c.-13G>C
ENST00000610538.4:c.-13G>C
ENST00000615910.4:n.105G>C
ENST00000617185.4:c.105G>C
ENST00000619485.4:c.-13G>C
ENST00000620739.4:c.-13G>C
ENST00000622645.4:c.-13G>C
ENST00000635293.1:c.-13G>C
NM_001126112.2:c.105G>C
NM_001126113.2:c.105G>C
NM_001126114.2:c.105G>C
NM_001126118.1:c.-13G>C
NM_001276695.1:c.-13G>C
NM_001276696.1:c.-13G>C
NM_001276760.1:c.-13G>C
NM_001276761.1:c.-13G>C
NM_001276695.2:c.-13G>C
NM_001276696.2:c.-13G>C
NM_001276760.2:c.-13G>C
NM_001276761.2:c.-13G>C
NM_000546.6:c.105G>C
NM_001126112.3:c.105G>C
NM_001126113.3:c.105G>C
NM_001126114.3:c.105G>C
NM_001126118.2:c.-13G>C
NM_001276695.3:c.-13G>C
NM_001276696.3:c.-13G>C
NM_001276760.3:c.-13G>C
NM_001276761.3:c.-13G>C
NC_000017.11:g.7676264C>G
CM000679.2:g.7676264C>G
NC_000017.10:g.7579582C>G
CM000679.1:g.7579582C>G
NC_000017.9:g.7520307C>G
NG_017013.2:g.16287G>C

Likely Benign

Met criteria codes 3
BS2_Supporting BS3 BP4
Not Met criteria codes 16
PM6 PM2 PM3 PM5 BS4 BS1 BP5 BP2 PS2 PS4 PS3 PS1 BA1 PP4 PP1 PP3

Evidence Links 2

Expert Panel

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 C0 or Class C15 (BP4). 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 2-7 60+ year old females without a cancer diagnosis (BS2_Supporting; internal laboratory contributor). In summary, TP53 c.105G>C (p.Leu35Phe) 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: BP4, BS3, BS2_supporting.
Met criteria codes
BS2_Supporting
3 F unaffected at age 60 from Invitae internal data
BS3
Kato: functional. Giacomelli: no DNE
No DNE PubMed:30224644
Functional PubMed:12826609
BP4
Align GVGD Class C0, BayesDel score = -0.0784742. No splicing effect (varSEAK, spliceAI)
Not Met criteria codes
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Present in 1 allele in gnomAD v2 (European non-Finnish)
PM3
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
from Invitae internal data: seen in one case co-occuring with a pathogenic potential mosaic TP53 variant in an individual with BC 50's + FHx BC and pancreatic ca >50
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
1 case meeting Chompret criteria from Invitae internal data
PS3
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
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
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
Approved on: 2020-09-17
Published on: 2021-06-16
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