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]

Variant: NM_001126115.1(TP53):c.182A>C (p.His61Pro)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA16603033

376612 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b7079914-1dfb-4bb9-8f67-f466a0532ac1

Approved on: 2019-08-28

Published on: 2020-01-24

HGVS expressions

NM_001126115.1:c.182A>C

NM_001126115.1(TP53):c.182A>C (p.His61Pro)

NC_000017.11:g.7674953T>G

CM000679.2:g.7674953T>G

NC_000017.10:g.7578271T>G

CM000679.1:g.7578271T>G

NC_000017.9:g.7518996T>G

NG_017013.2:g.17598A>C

ENST00000503591.2:c.578A>C

ENST00000508793.6:c.578A>C

ENST00000509690.6:c.182A>C

ENST00000514944.6:c.299A>C

ENST00000604348.6:c.557A>C

ENST00000269305.9:c.578A>C

ENST00000269305.8:c.578A>C

ENST00000359597.8:c.578A>C

ENST00000413465.6:c.578A>C

ENST00000420246.6:c.578A>C

ENST00000445888.6:c.578A>C

ENST00000455263.6:c.578A>C

ENST00000504290.5:c.182A>C

ENST00000504937.5:c.182A>C

ENST00000505014.5:n.834A>C

ENST00000509690.5:c.182A>C

ENST00000510385.5:c.182A>C

ENST00000514944.5:c.299A>C

ENST00000574684.1:n.67+100A>C

ENST00000610292.4:c.461A>C

ENST00000610538.4:c.461A>C

ENST00000610623.4:c.101A>C

ENST00000615910.4:c.545A>C

ENST00000617185.4:c.578A>C

ENST00000618944.4:c.101A>C

ENST00000619186.4:c.101A>C

ENST00000619485.4:c.461A>C

ENST00000620739.4:c.461A>C

ENST00000622645.4:c.461A>C

ENST00000635293.1:c.461A>C

NM_000546.5:c.578A>C

NM_001126112.2:c.578A>C

NM_001126113.2:c.578A>C

NM_001126114.2:c.578A>C

NM_001126116.1:c.182A>C

NM_001126117.1:c.182A>C

NM_001126118.1:c.461A>C

NM_001276695.1:c.461A>C

NM_001276696.1:c.461A>C

NM_001276697.1:c.101A>C

NM_001276698.1:c.101A>C

NM_001276699.1:c.101A>C

NM_001276760.1:c.461A>C

NM_001276761.1:c.461A>C

NM_001276695.2:c.461A>C

NM_001276696.2:c.461A>C

NM_001276697.2:c.101A>C

NM_001276698.2:c.101A>C

NM_001276699.2:c.101A>C

NM_001276760.2:c.461A>C

NM_001276761.2:c.461A>C

NM_000546.6:c.578A>C

NM_001126112.3:c.578A>C

NM_001126113.3:c.578A>C

NM_001126114.3:c.578A>C

NM_001126115.2:c.182A>C

NM_001126116.2:c.182A>C

NM_001126117.2:c.182A>C

NM_001126118.2:c.461A>C

NM_001276695.3:c.461A>C

NM_001276696.3:c.461A>C

NM_001276697.3:c.101A>C

NM_001276698.3:c.101A>C

NM_001276699.3:c.101A>C

NM_001276760.3:c.461A>C

NM_001276761.3:c.461A>C

Pathogenic

PS4_Supporting PM6 PP3_Moderate PM2_Supporting PS3

BP4

Evidence Links 2

Expert Panel

TP53 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

TP53 VCEP

This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has a BayesDel score > 0.16 and Align GVGD (Zebrafish) is Class 65 (PP3_Moderate). 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 2 probands meeting Chompret criteria (PS4_Supporting; PMID: 28369373, 20308654). Additionally, there is one proband with a de novo observation of a Li-Fraumeni syndrome core cancer under the age of 5 years without parental confirmation (PM6; PMID: 25584008). In summary, the clinical significance of TP53 c.578A>C; p.His193Pro is pathogenic for Li-Fraumeni syndrome: PM2_Supporting, PP3_Moderate, PS3, PS4_Supporting, PM6.

PS4_Supporting

2 probands meeting Chompret criteria = 1 point

This variant was reported in one proband with a choroid plexus tumor and adrenocorticol tumor at 1 yr and no family history. Proband = 0.5 point PubMed:20308654

Variant found in individual with STS (49), LC (54), Melanoma (55) meeting Chompret criteria. Proband = 0.5 PubMed:28369373

PM6

ACC patient with de novo variant w/o mention of parental confirmation. Proband = 1 point

PP3_Moderate

AGVGD score is C65 and BayesDel score is >0.16

PM2_Supporting

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS3

Functional allele according to T-A assays in IARC; colony formation assay showed decreased suppressed growth

BP4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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