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]
  • See Evidence submitted by expert panel for details.

Variant: NM_001126112.2(TP53):c.907A>G (p.Ser303Gly)

CA000491

142332 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 481b1f30-a3cc-4e41-8fac-e657737c7811
Approved on: 2021-05-07
Published on: 2021-06-16

HGVS expressions

NM_001126112.2:c.907A>G
NM_001126112.2(TP53):c.907A>G (p.Ser303Gly)
NC_000017.11:g.7673713T>C
CM000679.2:g.7673713T>C
NC_000017.10:g.7577031T>C
CM000679.1:g.7577031T>C
NC_000017.9:g.7517756T>C
NG_017013.2:g.18838A>G
ENST00000269305.9:c.907A>G
ENST00000269305.8:c.907A>G
ENST00000359597.8:n.907A>G
ENST00000413465.6:n.782+468A>G
ENST00000420246.6:c.907A>G
ENST00000445888.6:c.907A>G
ENST00000455263.6:c.907A>G
ENST00000504290.5:c.511A>G
ENST00000504937.5:c.511A>G
ENST00000509690.5:c.511A>G
ENST00000510385.5:c.511A>G
ENST00000610292.4:c.790A>G
ENST00000610538.4:c.790A>G
ENST00000610623.4:c.430A>G
ENST00000615910.4:n.874A>G
ENST00000617185.4:c.907A>G
ENST00000618944.4:c.430A>G
ENST00000619186.4:c.430A>G
ENST00000619485.4:c.790A>G
ENST00000620739.4:c.790A>G
ENST00000622645.4:c.790A>G
ENST00000635293.1:c.790A>G
NM_000546.5:c.907A>G
NM_001126113.2:c.907A>G
NM_001126114.2:c.907A>G
NM_001126115.1:c.511A>G
NM_001126116.1:c.511A>G
NM_001126117.1:c.511A>G
NM_001126118.1:c.790A>G
NM_001276695.1:c.790A>G
NM_001276696.1:c.790A>G
NM_001276697.1:c.430A>G
NM_001276698.1:c.430A>G
NM_001276699.1:c.430A>G
NM_001276760.1:c.790A>G
NM_001276761.1:c.790A>G
NM_001276695.2:c.790A>G
NM_001276696.2:c.790A>G
NM_001276697.2:c.430A>G
NM_001276698.2:c.430A>G
NM_001276699.2:c.430A>G
NM_001276760.2:c.790A>G
NM_001276761.2:c.790A>G
NM_000546.6:c.907A>G
NM_001126112.3:c.907A>G
NM_001126113.3:c.907A>G
NM_001126114.3:c.907A>G
NM_001126115.2:c.511A>G
NM_001126116.2:c.511A>G
NM_001126117.2:c.511A>G
NM_001126118.2:c.790A>G
NM_001276695.3:c.790A>G
NM_001276696.3:c.790A>G
NM_001276697.3:c.430A>G
NM_001276698.3:c.430A>G
NM_001276699.3:c.430A>G
NM_001276760.3:c.790A>G
NM_001276761.3:c.790A>G
More

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"
Met criteria codes 3
PM2_Supporting BS3 BP4
Not Met criteria codes 14
PS2 PS4 PS3 PS1 PP1 PP3 PM1 PM5 PM6 BA1 BS4 BS1 BS2 BP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). Transactivation assays show supertransactivation 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). In summary, TP53 c.907A>G (p.Ser303Gly) 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, BP4, PM2_Supporting.
Met criteria codes
PM2_Supporting
Absent from gnomAD
BS3
Kato supertrans; no evidence of DNE or LOF by Giacomelli; Kotler N/A
BP4
aGVGD = C0; BayesDel = -0.0726
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Observed 9+ times across clinical laboratories with no informative cases.
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
PP1
Observed 9+ times across clinical laboratories with no informative cases.
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not in cancerhotspots.com
PM5
S303N (ID: 230695, VUSx2) – not VCEP curated
PM6
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
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
BS2
Observed 9+ times across clinical laboratories with no informative cases.
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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