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

Variant: NM_000546.5(TP53):c.779C>A (p.Ser260Tyr)

CA10580921

231033 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 4cd6d688-6774-41c7-b590-7f3359f7d34c
Approved on: 2021-08-04
Published on: 2021-09-24

HGVS expressions

NM_000546.5:c.779C>A
NM_000546.5(TP53):c.779C>A (p.Ser260Tyr)
NC_000017.11:g.7674184G>T
CM000679.2:g.7674184G>T
NC_000017.10:g.7577502G>T
CM000679.1:g.7577502G>T
NC_000017.9:g.7518227G>T
NG_017013.2:g.18367C>A
ENST00000269305.9:c.779C>A
ENST00000269305.8:c.779C>A
ENST00000359597.8:n.779C>A
ENST00000413465.6:n.779C>A
ENST00000420246.6:c.779C>A
ENST00000445888.6:c.779C>A
ENST00000455263.6:c.779C>A
ENST00000504290.5:c.383C>A
ENST00000504937.5:c.383C>A
ENST00000509690.5:c.383C>A
ENST00000510385.5:c.383C>A
ENST00000610292.4:c.662C>A
ENST00000610538.4:c.662C>A
ENST00000610623.4:c.302C>A
ENST00000615910.4:n.746C>A
ENST00000617185.4:c.779C>A
ENST00000618944.4:c.302C>A
ENST00000619186.4:c.302C>A
ENST00000619485.4:c.662C>A
ENST00000620739.4:c.662C>A
ENST00000622645.4:c.662C>A
ENST00000635293.1:c.662C>A
NM_001126112.2:c.779C>A
NM_001126113.2:c.779C>A
NM_001126114.2:c.779C>A
NM_001126115.1:c.383C>A
NM_001126116.1:c.383C>A
NM_001126117.1:c.383C>A
NM_001126118.1:c.662C>A
NM_001276695.1:c.662C>A
NM_001276696.1:c.662C>A
NM_001276697.1:c.302C>A
NM_001276698.1:c.302C>A
NM_001276699.1:c.302C>A
NM_001276760.1:c.662C>A
NM_001276761.1:c.662C>A
NM_001276695.2:c.662C>A
NM_001276696.2:c.662C>A
NM_001276697.2:c.302C>A
NM_001276698.2:c.302C>A
NM_001276699.2:c.302C>A
NM_001276760.2:c.662C>A
NM_001276761.2:c.662C>A
NM_000546.6:c.779C>A
NM_001126112.3:c.779C>A
NM_001126113.3:c.779C>A
NM_001126114.3:c.779C>A
NM_001126115.2:c.383C>A
NM_001126116.2:c.383C>A
NM_001126117.2:c.383C>A
NM_001126118.2:c.662C>A
NM_001276695.3:c.662C>A
NM_001276696.3:c.662C>A
NM_001276697.3:c.302C>A
NM_001276698.3:c.302C>A
NM_001276699.3:c.302C>A
NM_001276760.3:c.662C>A
NM_001276761.3:c.662C>A

Likely Benign

Met criteria codes 2
BS3 BS2_Supporting
Not Met criteria codes 17
BS4 BS1 BP2 BP4 BP1 PS2 PS4 PS3 PS1 BA1 PP1 PP3 PP2 PM6 PM2 PM1 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
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 has been observed in 2-7 60+ year old females without a cancer diagnosis (BS2_Supporting; internal laboratory contributors). In summary, TP53 c.779C>A (p.Ser260Tyr) 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: BS3, BS2_supporting.
Met criteria codes
BS3
TA class: functional, p53WT_Nutlin-3_Z-score: 0.3167, p53NULL_Etoposide_Z-score: 0.5025
BS2_Supporting
Not in FLOSSIES, not in literature. 2 cases >60 years of age cancer free females in internal data from one lab
Not Met criteria codes
BS4
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
Align-GVGD Class C0, BayesDel 0.229798. No splicing effect: varSEAK class 1, SpliceAI acceptor loss 0.0, donor loss 0.0, acceptor gain 0.0, donor gain 0.0
BP1
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
PS4
not in literature, none in internal data
PS3
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
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Present in 1 (south Asian) allele in gnomAD v2.1.1
PM1
Not in a hotspot codon nor in cancerhotspots.org
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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