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

CA397849034

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 293a5c7a-2593-4a7d-afc2-9e06636238fe

Approved on: 2021-06-16

Published on: 2021-06-16

HGVS expressions

NM_001276761.2:c.-72C>A

ENST00000269305.9:c.46C>A

ENST00000269305.8:c.46C>A

ENST00000359597.8:n.46C>A

ENST00000413465.6:n.46C>A

ENST00000420246.6:c.46C>A

ENST00000445888.6:c.46C>A

ENST00000455263.6:c.46C>A

ENST00000503591.1:c.46C>A

ENST00000505014.5:n.185C>A

ENST00000508793.5:c.46C>A

ENST00000509690.5:c.-21-1313C>A

ENST00000514944.5:c.46C>A

ENST00000604348.5:c.46C>A

ENST00000610292.4:c.-189C>A

ENST00000610538.4:c.-72C>A

ENST00000615910.4:n.46C>A

ENST00000617185.4:c.46C>A

ENST00000619485.4:c.-72C>A

ENST00000620739.4:c.-72C>A

ENST00000622645.4:c.-72C>A

ENST00000635293.1:c.-72C>A

NM_000546.5:c.46C>A

NM_001126112.2:c.46C>A

NM_001126113.2:c.46C>A

NM_001126114.2:c.46C>A

NM_001126118.1:c.-189C>A

NM_001276695.1:c.-72C>A

NM_001276696.1:c.-72C>A

NM_001276760.1:c.-72C>A

NM_001276761.1:c.-72C>A

NM_001276695.2:c.-72C>A

NM_001276696.2:c.-72C>A

NM_001276760.2:c.-72C>A

NM_000546.6:c.46C>A

NM_001126112.3:c.46C>A

NM_001126113.3:c.46C>A

NM_001126114.3:c.46C>A

NM_001126118.2:c.-189C>A

NM_001276695.3:c.-72C>A

NM_001276696.3:c.-72C>A

NM_001276760.3:c.-72C>A

NM_001276761.3:c.-72C>A

NC_000017.11:g.7676549G>T

CM000679.2:g.7676549G>T

NC_000017.10:g.7579867G>T

CM000679.1:g.7579867G>T

NC_000017.9:g.7520592G>T

NG_017013.2:g.16002C>A

Uncertain Significance

PM2 BS3

PS2 PS4 PS1 PS3 PP1 PP3 PM6 PM5 PM1 BA1 BS2 BS4 BS1 BP2 BP4

Evidence Links 0

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). Transactivation assays show supertransactivation 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). In summary, the clinical significance of TP53 c.46C>A (p.Gln16Lys) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM2_Supporting, BS3.

PM2

Not in gnomAD

BS3

Supertransactivation on Kato (118.3%). No DNE or LOF on Giacomelli assay.

PS2

No reports in literature or internal data

PS4

No reports in literature or internal data

PS1

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

PS3

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

PP1

No reports in literature or internal data

PP3

AGVGD of C45 (pathogenic) but BayesDel of 0.1429 (benign). Conflicting scores so not met

PM6

No reports in literature or internal data

PM5

Two other variants in ClinVar, both VUS

PM1

Not a hotspot or in cancerhotspots.org

BA1

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

BS2

Not in FLOSSIES

BS4

No reports in literature or internal data

BS1

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

BP2

No reports in literature or internal data

BP4

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

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