The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

Variant: NM_000546.5(TP53):c.704A>G (p.Asn235Ser)

CA000343

127821 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: 38d9dfad-aa7b-409a-9fd8-3f6898fb8c57
Approved on: 2019-08-28
Published on: 2020-01-24

HGVS expressions

NM_000546.5:c.704A>G
NM_000546.5(TP53):c.704A>G (p.Asn235Ser)
NC_000017.11:g.7674259T>C
CM000679.2:g.7674259T>C
NC_000017.10:g.7577577T>C
CM000679.1:g.7577577T>C
NC_000017.9:g.7518302T>C
NG_017013.2:g.18292A>G
ENST00000503591.2:c.704A>G
ENST00000508793.6:c.704A>G
ENST00000509690.6:c.308A>G
ENST00000514944.6:c.425A>G
ENST00000604348.6:c.683A>G
ENST00000269305.9:c.704A>G
ENST00000269305.8:c.704A>G
ENST00000359597.8:c.704A>G
ENST00000413465.6:c.704A>G
ENST00000420246.6:c.704A>G
ENST00000445888.6:c.704A>G
ENST00000455263.6:c.704A>G
ENST00000504290.5:c.308A>G
ENST00000504937.5:c.308A>G
ENST00000509690.5:c.308A>G
ENST00000510385.5:c.308A>G
ENST00000514944.5:c.425A>G
ENST00000574684.1:n.99A>G
ENST00000610292.4:c.587A>G
ENST00000610538.4:c.587A>G
ENST00000610623.4:c.227A>G
ENST00000615910.4:c.671A>G
ENST00000617185.4:c.704A>G
ENST00000618944.4:c.227A>G
ENST00000619186.4:c.227A>G
ENST00000619485.4:c.587A>G
ENST00000620739.4:c.587A>G
ENST00000622645.4:c.587A>G
ENST00000635293.1:c.587A>G
NM_001126112.2:c.704A>G
NM_001126113.2:c.704A>G
NM_001126114.2:c.704A>G
NM_001126115.1:c.308A>G
NM_001126116.1:c.308A>G
NM_001126117.1:c.308A>G
NM_001126118.1:c.587A>G
NM_001276695.1:c.587A>G
NM_001276696.1:c.587A>G
NM_001276697.1:c.227A>G
NM_001276698.1:c.227A>G
NM_001276699.1:c.227A>G
NM_001276760.1:c.587A>G
NM_001276761.1:c.587A>G
NM_001276695.2:c.587A>G
NM_001276696.2:c.587A>G
NM_001276697.2:c.227A>G
NM_001276698.2:c.227A>G
NM_001276699.2:c.227A>G
NM_001276760.2:c.587A>G
NM_001276761.2:c.587A>G
NM_000546.6:c.704A>G
NM_001126112.3:c.704A>G
NM_001126113.3:c.704A>G
NM_001126114.3:c.704A>G
NM_001126115.2:c.308A>G
NM_001126116.2:c.308A>G
NM_001126117.2:c.308A>G
NM_001126118.2:c.587A>G
NM_001276695.3:c.587A>G
NM_001276696.3:c.587A>G
NM_001276697.3:c.227A>G
NM_001276698.3:c.227A>G
NM_001276699.3:c.227A>G
NM_001276760.3:c.587A>G
NM_001276761.3:c.587A>G
More

Benign

Met criteria codes 6
BS1 BS4 BS3 BP4 BP2 BS2_Supporting

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
This variant has a minor allele frequency of 0.0003175 (0.03%, 41/129,118 alleles) in the European (non-Finnish) subpopulation of the gnomAD cohort (BS1). The 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). This variant also segregates to the opposite side of a family who meets Li-Fraumeni syndrome criteria. (BS4; PMID: 17318340). The proband in this same family has a pathogenic variant (TP53 c.560-1G>A) in trans with this variant. (BP2; PMID: 17318340). Finally, this variant has been observed in at least 4 60+ year old females without a cancer diagnosis (BS2_Supporting; FLOSSIES database - https://whi.color.com).In summary, TP53 c.704A>G; p.Asn235Ser meets criteria to be classified as benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS1, BP4, BS3, BS4, BP2, BS2_Supporting.
Met criteria codes
BS1
0.05% in Finnish population with 14 alleles
BS4
Asn235Ser did not track w/ cancer in a family meeting criteria for LFS, who also had a different pathogenic variant that did track with cancer.
BS3
Functional variant on T-A assays according to Kato, et al and no evidence of DNE or LOF in Giacomelli, et al data

BP4
BayesDel & AGVGD are concordant
BP2
Asn235Ser did not track w/ cancer in a family meeting criteria for LFS, who also had a different pathogenic variant that did track with cancer.
BS2_Supporting
Variant observed in 4 individuals from the FLOSSIES data.
Curation History
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