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

Variant: NM_001126112.2(TP53):c.149T>C (p.Ile50Thr)

CA337284

216464 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: dfaea420-dc78-42fc-8466-b64b8fbcf7ed

HGVS expressions

NM_001126112.2:c.149T>C

NM_001126112.2(TP53):c.149T>C (p.Ile50Thr)

ENST00000269305.9:c.149T>C

ENST00000269305.8:c.149T>C

ENST00000359597.8:n.149T>C

ENST00000413465.6:n.149T>C

ENST00000420246.6:c.149T>C

ENST00000445888.6:c.149T>C

ENST00000455263.6:c.149T>C

ENST00000503591.1:c.149T>C

ENST00000505014.5:n.405T>C

ENST00000508793.5:c.149T>C

ENST00000509690.5:c.-21-984T>C

ENST00000514944.5:c.96+162T>C

ENST00000604348.5:c.149T>C

ENST00000610292.4:c.32T>C

ENST00000610538.4:c.32T>C

ENST00000615910.4:n.149T>C

ENST00000617185.4:c.149T>C

ENST00000619485.4:c.32T>C

ENST00000620739.4:c.32T>C

ENST00000622645.4:c.32T>C

ENST00000635293.1:c.32T>C

NM_000546.5:c.149T>C

NM_001126113.2:c.149T>C

NM_001126114.2:c.149T>C

NM_001126118.1:c.32T>C

NM_001276695.1:c.32T>C

NM_001276696.1:c.32T>C

NM_001276760.1:c.32T>C

NM_001276761.1:c.32T>C

NM_001276695.2:c.32T>C

NM_001276696.2:c.32T>C

NM_001276760.2:c.32T>C

NM_001276761.2:c.32T>C

NM_000546.6:c.149T>C

NM_001126112.3:c.149T>C

NM_001126113.3:c.149T>C

NM_001126114.3:c.149T>C

NM_001126118.2:c.32T>C

NM_001276695.3:c.32T>C

NM_001276696.3:c.32T>C

NM_001276760.3:c.32T>C

NM_001276761.3:c.32T>C

NC_000017.11:g.7676220A>G

CM000679.2:g.7676220A>G

NC_000017.10:g.7579538A>G

CM000679.1:g.7579538A>G

NC_000017.9:g.7520263A>G

NG_017013.2:g.16331T>C

Likely Benign

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

BS3_Supporting PM2_Supporting BP4

PS4 PM1 PM5 BS2

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). Transactivation assays show a partially functional variant 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_Supporting; PMID: 12826609, 30224644). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). In summary, TP53 c.149T>C (p.Ile50Thr) 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_Supporting, BP4.

BS3_Supporting

Kato (PMID: 12826609): partially functional, Giacomelli (PMID: 30224644): noDNE+noLOF

noDNE+noLOF PubMed:30224644

partially functional PubMed:12826609

PM2_Supporting

Absent from gnomAD

BP4

A-GVGD: C0. BayesDel: -0.0655.

PS4

Seen as germline in an individual with B-Lineage ALL E2A-PBX1 Subtype (PMID: 26580448)

PM1

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

PM5

p.Ile50Asn is VUS in ClinVar

BS2

1 female unaffected with cancer at age 60 (SCV000254627.6). 1 female unaffected with cancer at age 60 (SCV000274284.4)

Approved on: 2021-04-02

Published on: 2021-06-16

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.