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

CA397836609

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6dab48cd-422d-4d98-9cea-3e99b23c6a4b

Approved on: 2021-06-16

Published on: 2021-06-16

HGVS expressions

NM_001276761.2:c.749T>C

ENST00000269305.9:c.866T>C

ENST00000269305.8:c.866T>C

ENST00000359597.8:n.866T>C

ENST00000413465.6:n.782+427T>C

ENST00000420246.6:c.866T>C

ENST00000445888.6:c.866T>C

ENST00000455263.6:c.866T>C

ENST00000504290.5:c.470T>C

ENST00000504937.5:c.470T>C

ENST00000509690.5:c.470T>C

ENST00000510385.5:c.470T>C

ENST00000610292.4:c.749T>C

ENST00000610538.4:c.749T>C

ENST00000610623.4:c.389T>C

ENST00000615910.4:n.833T>C

ENST00000617185.4:c.866T>C

ENST00000618944.4:c.389T>C

ENST00000619186.4:c.389T>C

ENST00000619485.4:c.749T>C

ENST00000620739.4:c.749T>C

ENST00000622645.4:c.749T>C

ENST00000635293.1:c.749T>C

NM_000546.5:c.866T>C

NM_001126112.2:c.866T>C

NM_001126113.2:c.866T>C

NM_001126114.2:c.866T>C

NM_001126115.1:c.470T>C

NM_001126116.1:c.470T>C

NM_001126117.1:c.470T>C

NM_001126118.1:c.749T>C

NM_001276695.1:c.749T>C

NM_001276696.1:c.749T>C

NM_001276697.1:c.389T>C

NM_001276698.1:c.389T>C

NM_001276699.1:c.389T>C

NM_001276760.1:c.749T>C

NM_001276761.1:c.749T>C

NM_001276695.2:c.749T>C

NM_001276696.2:c.749T>C

NM_001276697.2:c.389T>C

NM_001276698.2:c.389T>C

NM_001276699.2:c.389T>C

NM_001276760.2:c.749T>C

NM_000546.6:c.866T>C

NM_001126112.3:c.866T>C

NM_001126113.3:c.866T>C

NM_001126114.3:c.866T>C

NM_001126115.2:c.470T>C

NM_001126116.2:c.470T>C

NM_001126117.2:c.470T>C

NM_001126118.2:c.749T>C

NM_001276695.3:c.749T>C

NM_001276696.3:c.749T>C

NM_001276697.3:c.389T>C

NM_001276698.3:c.389T>C

NM_001276699.3:c.389T>C

NM_001276760.3:c.749T>C

NM_001276761.3:c.749T>C

NC_000017.11:g.7673754A>G

CM000679.2:g.7673754A>G

NC_000017.10:g.7577072A>G

CM000679.1:g.7577072A>G

NC_000017.9:g.7517797A>G

NG_017013.2:g.18797T>C

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"

BS3 BP4 PM2_Supporting

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

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 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 a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). In summary, TP53 c.866T>C (p.Leu289Pro) 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: PM2_Supporting, BS3, BP4. PM2_Supporting should not be considered conflicting evidence as there is sufficient evidence for classification as Likely Benign

BS3

Kato just functional at 75.45%. Giacomelli retained function with no DNE or LOF.

BP4

AGVGD of C0 and BayesDel of -0.0138

PM2_Supporting

Variant absent from gnomAD (not filtered)

BS4

No cases in literature or internal data

BS1

Not present in gnomAD

BS2

Not in FLOSSIES

BP2

No cases in literature or internal data

PS2

No cases in literature or internal data

PS4

Not observed in literature or internal data

PS3

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

PS1

Two other variants in ClinVar: one benign, one VUS

PP1

No cases in literature or internal data

PP3

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

PM1

Not a hotspot codon and not in cancer hotspots

PM5

Two other variants in ClinVar: one benign, one VUS

PM6

No cases in literature or internal data

BA1

Not present in gnomAD

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.