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.636del (p.Arg213fs)

CA248848

218342 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 43ea40bf-abe3-4125-8861-85030e6c815c

HGVS expressions

NM_001126112.2:c.636del

NM_001126112.2(TP53):c.636del (p.Arg213fs)

ENST00000269305.9:c.636del

ENST00000269305.8:c.636del

ENST00000359597.8:n.636del

ENST00000413465.6:n.636del

ENST00000420246.6:c.636del

ENST00000445888.6:c.636del

ENST00000455263.6:c.636del

ENST00000504290.5:c.240del

ENST00000504937.5:c.240del

ENST00000505014.5:n.892del

ENST00000509690.5:c.240del

ENST00000510385.5:c.240del

ENST00000514944.5:c.357del

ENST00000574684.1:n.67+158del

ENST00000610292.4:c.519del

ENST00000610538.4:c.519del

ENST00000610623.4:c.159del

ENST00000615910.4:n.603del

ENST00000617185.4:c.636del

ENST00000618944.4:c.159del

ENST00000619186.4:c.159del

ENST00000619485.4:c.519del

ENST00000620739.4:c.519del

ENST00000622645.4:c.519del

ENST00000635293.1:c.519del

NM_000546.5:c.636del

NM_001126113.2:c.636del

NM_001126114.2:c.636del

NM_001126115.1:c.240del

NM_001126116.1:c.240del

NM_001126117.1:c.240del

NM_001126118.1:c.519del

NM_001276695.1:c.519del

NM_001276696.1:c.519del

NM_001276697.1:c.159del

NM_001276698.1:c.159del

NM_001276699.1:c.159del

NM_001276760.1:c.519del

NM_001276761.1:c.519del

NM_001276695.2:c.519del

NM_001276696.2:c.519del

NM_001276697.2:c.159del

NM_001276698.2:c.159del

NM_001276699.2:c.159del

NM_001276760.2:c.519del

NM_001276761.2:c.519del

NM_000546.6:c.636del

NM_001126112.3:c.636del

NM_001126113.3:c.636del

NM_001126114.3:c.636del

NM_001126115.2:c.240del

NM_001126116.2:c.240del

NM_001126117.2:c.240del

NM_001126118.2:c.519del

NM_001276695.3:c.519del

NM_001276696.3:c.519del

NM_001276697.3:c.159del

NM_001276698.3:c.159del

NM_001276699.3:c.159del

NM_001276760.3:c.519del

NM_001276761.3:c.519del

NC_000017.11:g.7674898del

CM000679.2:g.7674898del

NC_000017.10:g.7578216del

CM000679.1:g.7578216del

NC_000017.9:g.7518941del

NG_017013.2:g.17656del

Pathogenic

PVS1 PS4_Supporting PM2_Supporting

PP1 BA1 BS2 BS1

Evidence Links 0

Expert Panel

TP53 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

TP53 VCEP

The p.R213fs variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in 2 probands meeting Chompret criteria (PS4_Supporting; PMID: 11370630, NIH). In summary, TP53 c.636del (p.R213fs) 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, PM2_Supporting, PS4_Supporting.

PVS1

Frameshift in exon 6 of 11 in core/DNA-binding domain

PS4_Supporting

NIH cohort: Chompret (0.5 pts); PMID 11370630: Chompret (0.5 pts) Total = 1 pts.

PM2_Supporting

Absent from gnomAD (non-cancer). Supporting per VCEP

PP1

2 meioses in one family. Need 3+ to count.

BA1

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

BS2

Absent from FLOSSIES. Internal lab data not provided for evaluation.

BS1

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

Approved on: 2020-09-04

Published on: 2021-06-16

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