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]

Link to SEPIO compliant JSON-LD document

CA397848094

638853 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b8bc495e-5c4e-42b1-89c3-4e8dbb41b60b

HGVS expressions

NM_001276761.1:c.-21-1G>A

NM_000546.5:c.97-1G>A

NM_001126112.2:c.97-1G>A

NM_001126113.2:c.97-1G>A

NM_001126114.2:c.97-1G>A

NM_001126118.1:c.-21-1G>A

NM_001276695.1:c.-21-1G>A

NM_001276696.1:c.-21-1G>A

NM_001276760.1:c.-21-1G>A

NM_001276695.2:c.-21-1G>A

NM_001276696.2:c.-21-1G>A

NM_001276760.2:c.-21-1G>A

NM_001276761.2:c.-21-1G>A

ENST00000269305.8:c.97-1G>A

ENST00000359597.8:n.97-1G>A

ENST00000413465.6:n.97-1G>A

ENST00000420246.6:c.97-1G>A

ENST00000445888.6:c.97-1G>A

ENST00000455263.6:c.97-1G>A

ENST00000503591.1:c.97-1G>A

ENST00000505014.5:n.353-1G>A

ENST00000508793.5:c.97-1G>A

ENST00000509690.5:c.-21-1037G>A

ENST00000514944.5:c.96+109G>A

ENST00000604348.5:c.97-1G>A

ENST00000610292.4:c.-21-1G>A

ENST00000610538.4:c.-21-1G>A

ENST00000615910.4:n.97-1G>A

ENST00000617185.4:c.97-1G>A

ENST00000619485.4:c.-21-1G>A

ENST00000620739.4:c.-21-1G>A

ENST00000622645.4:c.-21-1G>A

ENST00000635293.1:c.-21-1G>A

NC_000017.11:g.7676273C>T

CM000679.2:g.7676273C>T

NC_000017.10:g.7579591C>T

CM000679.1:g.7579591C>T

NC_000017.9:g.7520316C>T

NG_017013.2:g.16278G>A

Likely Pathogenic

PM2_Supporting PVS1_Strong PS4_Supporting

Evidence Links 1

Expert Panel

TP53 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

TP53 VCEP

The c.97-1G>A is canonical splice variant predicted to result in a truncated or absent protein (PVS1_Strong). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least 1 proband meeting Classic Li-Fraumeni syndrome criteria (PS4_Supporting; PMID: 9792154). In summary, TP53 c.97-1G>A meets criteria to be classified as pathogenic for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PVS1_Strong, PM2_Supporting, PS4_Supporting.

PM2_Supporting

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

PVS1_Strong

canonical splice variant

PS4_Supporting

1 proband meeting Classic LFS = 1 point

Proband with osteosarcoma at age 15. Maternal uncle with leukemia at age 16. Maternal aunt with sarcoma at age 29. Maternal grandmother with a fibro- and osteosarcoma at ages 43 & 33. Multiple additional relatives w/cancer reported. Proband = 1 point PubMed:9792154

Approved on: 2019-08-28

Published on: 2020-01-24

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