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

CA248848

218342 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

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

Approved on: 2020-09-04

Published on: 2021-06-16

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

• Met criteria codes: PS4_Supporting PVS1 PM2_Supporting

• Not Met criteria codes: BA1 BS2 BS1 PP1

Expert Panel

TP53 VCEP

Criteria Specification Information

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.

Met criteria codes

• PS4_Supporting: NIH cohort: Chompret (0.5 pts); PMID 11370630: Chompret (0.5 pts) Total = 1 pts.
• PVS1: Frameshift in exon 6 of 11 in core/DNA-binding domain
• PM2_Supporting: Absent from gnomAD (non-cancer). Supporting per VCEP

Not Met criteria codes

• 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
• PP1: 2 meioses in one family. Need 3+ to count.