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]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

Variant: NM_000546.6(TP53):c.188C>G (p.Ala63Gly)

CA10580957

229693 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e2b86e34-c2dd-4cfe-97f2-92af3ac253cc
Approved on: 2021-08-05
Published on: 2021-09-24

HGVS expressions

NM_000546.6:c.188C>G
NM_000546.6(TP53):c.188C>G (p.Ala63Gly)
ENST00000269305.9:c.188C>G
ENST00000269305.8:c.188C>G
ENST00000359597.8:n.188C>G
ENST00000413465.6:n.188C>G
ENST00000420246.6:c.188C>G
ENST00000445888.6:c.188C>G
ENST00000455263.6:c.188C>G
ENST00000503591.1:c.188C>G
ENST00000505014.5:n.444C>G
ENST00000508793.5:c.188C>G
ENST00000509690.5:c.-21-945C>G
ENST00000514944.5:c.96+201C>G
ENST00000604348.5:c.188C>G
ENST00000610292.4:c.71C>G
ENST00000610538.4:c.71C>G
ENST00000615910.4:n.188C>G
ENST00000617185.4:c.188C>G
ENST00000619485.4:c.71C>G
ENST00000620739.4:c.71C>G
ENST00000622645.4:c.71C>G
ENST00000635293.1:c.71C>G
NM_000546.5:c.188C>G
NM_001126112.2:c.188C>G
NM_001126113.2:c.188C>G
NM_001126114.2:c.188C>G
NM_001126118.1:c.71C>G
NM_001276695.1:c.71C>G
NM_001276696.1:c.71C>G
NM_001276760.1:c.71C>G
NM_001276761.1:c.71C>G
NM_001276695.2:c.71C>G
NM_001276696.2:c.71C>G
NM_001276760.2:c.71C>G
NM_001276761.2:c.71C>G
NM_001126112.3:c.188C>G
NM_001126113.3:c.188C>G
NM_001126114.3:c.188C>G
NM_001126118.2:c.71C>G
NM_001276695.3:c.71C>G
NM_001276696.3:c.71C>G
NM_001276760.3:c.71C>G
NM_001276761.3:c.71C>G
NC_000017.11:g.7676181G>C
CM000679.2:g.7676181G>C
NC_000017.10:g.7579499G>C
CM000679.1:g.7579499G>C
NC_000017.9:g.7520224G>C
NG_017013.2:g.16370C>G

Likely Benign

Met criteria codes 3
BS2_Supporting BP4 BS3
Not Met criteria codes 14
PP1 PP3 PS2 PS4 PS3 PS1 PM1 PM5 PM6 PM2 BA1 BP2 BS4 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
Transactivation assays show retained/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). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). 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.188C>G (p.Ala63Gly) meets criteria for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3, BP4, BS2_Supporting.
Met criteria codes
BS2_Supporting
Not found in FLOSSIES database. Two women 60+ with no cancer reported by Ambry: Organization ID: 61756 internal data. One woman 60+ years with no cancer reported by Color: Organization ID: 505849 internal data. No women 60+ with no cancer by GeneDx: Organization ID: 26957 internal data. Three women 60+ with no cancer by Invitae: Organization ID: 500031 internal data.
BP4
Fortuno (PMID: 29775997) Align-GVGD Class: C0: Tolerated; Bayes-del: -0.155932;VarSEAK: Class 1 (no splicing effect); ; SpliceAI Δ=0.39 (no effect)
BS3
Giacomelli (PMID: 30224644): Nutlin = -0.08558877498; Giacomelli Toposide = 0.456671067; N/A in Kotler: (PMID: 29979965); Kato (PMID: 12826609): Transactivation assay = 75.3. No DNE + No LOF + functional. These assays combine to a BS3 evidence code.
Not Met criteria codes
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Variant detected in a male diagnosed with HYPERdiploid ALL at age 4.5 (PMID: 29300620). No criteria met to score phenotype points.
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
PM1
Not in a hotspot codon. Not found in cancerhotspots.
PM5
Codon 63 has not been reviewed by the TP53 VCEP as of 1/2021
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
One allele (European non-Finnish) present in gnomAD v2.1.1 (non-cancer). Allele frequency: 1/15408= 0.00006490
BA1
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
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
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.