Variant: NM_000546.5(TP53):c.329G>A (p.Arg110His)

CA000123

127808 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 00b45dfa-19f3-45de-975a-7b43bbc2be44

Approved on: 2020-08-11

Published on: 2020-08-14

HGVS expressions

NM_000546.5:c.329G>A
NM_000546.5(TP53):c.329G>A (p.Arg110His)
NC_000017.11:g.7676040C>T
CM000679.2:g.7676040C>T
NC_000017.10:g.7579358C>T
CM000679.1:g.7579358C>T
NC_000017.9:g.7520083C>T
NG_017013.2:g.16511G>A
ENST00000503591.2:c.329G>A
ENST00000508793.6:c.329G>A
ENST00000509690.6:c.-21-804G>A
ENST00000514944.6:c.96+342G>A
ENST00000604348.6:c.329G>A
ENST00000269305.9:c.329G>A
ENST00000269305.8:c.329G>A
ENST00000359597.8:c.329G>A
ENST00000413465.6:c.329G>A
ENST00000420246.6:c.329G>A
ENST00000445888.6:c.329G>A
ENST00000455263.6:c.329G>A
ENST00000503591.1:c.329G>A
ENST00000505014.5:n.585G>A
ENST00000508793.5:c.329G>A
ENST00000509690.5:c.-21-804G>A
ENST00000514944.5:c.96+342G>A
ENST00000604348.5:c.329G>A
ENST00000610292.4:c.212G>A
ENST00000610538.4:c.212G>A
ENST00000615910.4:c.329G>A
ENST00000617185.4:c.329G>A
ENST00000619485.4:c.212G>A
ENST00000620739.4:c.212G>A
ENST00000622645.4:c.212G>A
ENST00000635293.1:c.212G>A
NM_001126112.2:c.329G>A
NM_001126113.2:c.329G>A
NM_001126114.2:c.329G>A
NM_001126118.1:c.212G>A
NM_001276695.1:c.212G>A
NM_001276696.1:c.212G>A
NM_001276760.1:c.212G>A
NM_001276761.1:c.212G>A
NM_001276695.2:c.212G>A
NM_001276696.2:c.212G>A
NM_001276760.2:c.212G>A
NM_001276761.2:c.212G>A
NM_000546.6:c.329G>A
NM_001126112.3:c.329G>A
NM_001126113.3:c.329G>A
NM_001126114.3:c.329G>A
NM_001126118.2:c.212G>A
NM_001276695.3:c.212G>A
NM_001276696.3:c.212G>A
NM_001276760.3:c.212G>A
NM_001276761.3:c.212G>A

Likely Benign

• Met criteria codes: BS3_Supporting BP4 BS2_Supporting

• Not Met criteria codes: BA1 BS1 BS4 BP5 BP2 PS1 PS2 PS3 PS4 PP1 PP3 PP4 PM1 PM5 PM6 PM2

Expert Panel

TP53 VCEP

Criteria Specification Information

Evidence submitted by expert panel

TP53 VCEP

This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). 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 been observed in 2-7 60+ year old females without a cancer diagnosis (BS2_Supporting; Internal laboratory contributor.) In summary, TP53 c.329G>A (p.Arg110His) 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, BS3_Supporting, BS2_Supporting.

Met criteria codes

• BS3_Supporting: Partially functional variant + no_DNE + no_LOF
• BP4: AGVGD C0 and BayeDel 0.072
• BS2_Supporting: Not found in Flossies. Lab has 7 female cases that were cancer free at age 60 (SCV000184511.5).

Not Met criteria codes

• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: GeneDx has one case that meets Chompret (0.5 points) (SCV000149628.14). Identified in the literature in several women with breast cancer, one at age 32, two other reports with ages unconfirmed. (PMID: 23580068, 26976419, 2952266). Not enough points to meet.
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: AGVGD C0 and BayeDel 0.072
• PP4: Do not use rule
• PM1: Not in cancerhotpsots or designated hotspot
• PM5: Grantham score is 29. Three other variants found in codon have higher Grantham scores, 102, 103, and 108
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: 13 alleles in gnomAD