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]
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  • See Evidence submitted by expert panel for details.

Variant: NM_001126112.2(TP53):c.145G>C (p.Asp49His)

CA000057

135948 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 3ae5f394-d710-4984-8d13-7c585ade67dc
Approved on: 2022-01-10
Published on: 2022-01-10

HGVS expressions

NM_001126112.2:c.145G>C
NM_001126112.2(TP53):c.145G>C (p.Asp49His)
NC_000017.11:g.7676224C>G
CM000679.2:g.7676224C>G
NC_000017.10:g.7579542C>G
CM000679.1:g.7579542C>G
NC_000017.9:g.7520267C>G
NG_017013.2:g.16327G>C
ENST00000269305.9:c.145G>C
ENST00000269305.8:c.145G>C
ENST00000359597.8:n.145G>C
ENST00000413465.6:n.145G>C
ENST00000420246.6:c.145G>C
ENST00000445888.6:c.145G>C
ENST00000455263.6:c.145G>C
ENST00000503591.1:c.145G>C
ENST00000505014.5:n.401G>C
ENST00000508793.5:c.145G>C
ENST00000509690.5:c.-21-988G>C
ENST00000514944.5:c.96+158G>C
ENST00000604348.5:c.145G>C
ENST00000610292.4:c.28G>C
ENST00000610538.4:c.28G>C
ENST00000615910.4:n.145G>C
ENST00000617185.4:c.145G>C
ENST00000619485.4:c.28G>C
ENST00000620739.4:c.28G>C
ENST00000622645.4:c.28G>C
ENST00000635293.1:c.28G>C
NM_000546.5:c.145G>C
NM_001126113.2:c.145G>C
NM_001126114.2:c.145G>C
NM_001126118.1:c.28G>C
NM_001276695.1:c.28G>C
NM_001276696.1:c.28G>C
NM_001276760.1:c.28G>C
NM_001276761.1:c.28G>C
NM_001276695.2:c.28G>C
NM_001276696.2:c.28G>C
NM_001276760.2:c.28G>C
NM_001276761.2:c.28G>C
NM_000546.6:c.145G>C
NM_001126112.3:c.145G>C
NM_001126113.3:c.145G>C
NM_001126114.3:c.145G>C
NM_001126118.2:c.28G>C
NM_001276695.3:c.28G>C
NM_001276696.3:c.28G>C
NM_001276760.3:c.28G>C
NM_001276761.3:c.28G>C
NM_000546.6(TP53):c.145G>C (p.Asp49His)

Likely Benign

Met criteria codes 2
BS2_Supporting BP4
Not Met criteria codes 20
PM6 PM2 BA1 PM3 PM1 PM5 BS4 BS3 BS1 BP5 BP2 BP1 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2

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). 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.125G>C (p.D49H) 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, BS2_Supporting.
Met criteria codes
BS2_Supporting
3 female individuals cancer free by age 60 observed with this variant.
BP4
BayesDel -0.03 and AGVGD is C0
Not Met criteria codes
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
1 allele present in non-cancer dataset. Must be absent to apply PM2.
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not present in cancerhotspots.org
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
BS3
Kato et al shows non functional transactivation, but Giacomelli shows no DN and no loss of growth suppression.
This variant shows non-functional transactivation in yeast studies. PubMed:12826609
This variant shows no dominant negative effect and no loss of function. PubMed:30224644
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
Not used for TP53
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No individuals meeting LFS or Chompret criteira.
PS3
Kato et al shows non functional transactivation, but Giacomelli shows no DN and no loss of growth suppression.
This variant shows non-functional transactivation in yeast studies. PubMed:12826609
This variant shows no dominant negative effect and no loss of function. PubMed:30224644
PS1
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
PP2
Not used for TP53
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