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_000546.5(TP53):c.892G>A (p.Glu298Lys)

CA000483

141483 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8fb68094-5560-49d6-a48b-2a63d4e67265

HGVS expressions

NM_000546.5:c.892G>A

NM_000546.5(TP53):c.892G>A (p.Glu298Lys)

NC_000017.11:g.7673728C>T

CM000679.2:g.7673728C>T

NC_000017.10:g.7577046C>T

CM000679.1:g.7577046C>T

NC_000017.9:g.7517771C>T

NG_017013.2:g.18823G>A

NM_001126112.2:c.892G>A

NM_001126113.2:c.892G>A

NM_001126114.2:c.892G>A

NM_001126115.1:c.496G>A

NM_001126116.1:c.496G>A

NM_001126117.1:c.496G>A

NM_001126118.1:c.775G>A

NM_001276695.1:c.775G>A

NM_001276696.1:c.775G>A

NM_001276697.1:c.415G>A

NM_001276698.1:c.415G>A

NM_001276699.1:c.415G>A

NM_001276760.1:c.775G>A

NM_001276761.1:c.775G>A

ENST00000269305.8:c.892G>A

ENST00000359597.8:n.892G>A

ENST00000413465.6:n.782+453G>A

ENST00000420246.6:c.892G>A

ENST00000445888.6:c.892G>A

ENST00000455263.6:c.892G>A

ENST00000504290.5:c.496G>A

ENST00000504937.5:c.496G>A

ENST00000509690.5:c.496G>A

ENST00000510385.5:c.496G>A

ENST00000610292.4:c.775G>A

ENST00000610538.4:c.775G>A

ENST00000610623.4:c.415G>A

ENST00000615910.4:n.859G>A

ENST00000617185.4:c.892G>A

ENST00000618944.4:c.415G>A

ENST00000619186.4:c.415G>A

ENST00000619485.4:c.775G>A

ENST00000620739.4:c.775G>A

ENST00000622645.4:c.775G>A

ENST00000635293.1:c.775G>A

Likely Benign

BP4 BS3

Evidence Links 1

Expert Panel

TP53 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

TP53 VCEP

This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). Additionally, 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). In summary, TP53 c.892G>A; p.Glu298Lys 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: BP4 and BS3.

BP4

BayesDel & AGVGD are concordant

BS3

Functional variant on T-A assays according to Kato, et al and no evidence of DNE or LOF in Giacomelli, et al data

No evidence of DNE or LOF in Giacomelli, et al data PubMed:30224644

Approved on: 2019-08-28

Published on: 2020-01-24

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