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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  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000546.6(TP53):c.206C>G (p.Ala69Gly)

CA10580956

230112 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 521a9719-6db1-4bce-9eb7-cd771b563238
Approved on: 2024-08-05
Published on: 2024-08-05

HGVS expressions

NM_000546.6:c.206C>G
NM_000546.6(TP53):c.206C>G (p.Ala69Gly)
NC_000017.11:g.7676163G>C
CM000679.2:g.7676163G>C
NC_000017.10:g.7579481G>C
CM000679.1:g.7579481G>C
NC_000017.9:g.7520206G>C
NG_017013.2:g.16388C>G
ENST00000503591.2:c.206C>G
ENST00000508793.6:c.206C>G
ENST00000509690.6:c.-21-927C>G
ENST00000514944.6:c.96+219C>G
ENST00000604348.6:c.206C>G
ENST00000269305.9:c.206C>G
ENST00000269305.8:c.206C>G
ENST00000359597.8:c.206C>G
ENST00000413465.6:c.206C>G
ENST00000420246.6:c.206C>G
ENST00000445888.6:c.206C>G
ENST00000455263.6:c.206C>G
ENST00000503591.1:c.206C>G
ENST00000505014.5:n.462C>G
ENST00000508793.5:c.206C>G
ENST00000509690.5:c.-21-927C>G
ENST00000514944.5:c.96+219C>G
ENST00000604348.5:c.206C>G
ENST00000610292.4:c.89C>G
ENST00000610538.4:c.89C>G
ENST00000615910.4:c.206C>G
ENST00000617185.4:c.206C>G
ENST00000619485.4:c.89C>G
ENST00000620739.4:c.89C>G
ENST00000622645.4:c.89C>G
ENST00000635293.1:c.89C>G
NM_000546.5:c.206C>G
NM_001126112.2:c.206C>G
NM_001126113.2:c.206C>G
NM_001126114.2:c.206C>G
NM_001126118.1:c.89C>G
NM_001276695.1:c.89C>G
NM_001276696.1:c.89C>G
NM_001276760.1:c.89C>G
NM_001276761.1:c.89C>G
NM_001276695.2:c.89C>G
NM_001276696.2:c.89C>G
NM_001276760.2:c.89C>G
NM_001276761.2:c.89C>G
NM_001126112.3:c.206C>G
NM_001126113.3:c.206C>G
NM_001126114.3:c.206C>G
NM_001126118.2:c.89C>G
NM_001276695.3:c.89C>G
NM_001276696.3:c.89C>G
NM_001276760.3:c.89C>G
NM_001276761.3:c.89C>G

Uncertain Significance

Met criteria codes 2
BP4 PM2_Supporting
Not Met criteria codes 13
BA1 BS2 BS4 BS3 BS1 PS2 PS4 PS1 PS3 PP4 PP1 PM1 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
The NM_000546.6 :c.206C>G variant in TP53 is a missense variant predicted to cause substitution of alanine by glycine at amino acid 69 (p.Ala69Gly). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). Computational predictor scores (BayesDel = -0.1612; Align GVGD Class C0) are below the recommended thresholds (BayesDel ≤ -0.008 and an Align GVGD Class ≤ 55), evidence that does not predict a damaging effect on TP53 via protein change. SpliceAI predicts that the variant has no impact on splicing (BP4_Moderate). Due to conflicting evidence, this variant is classified as a variant of unknown significance for Li Fraumeni Syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: PM2_Supporting, BP4_Moderate. (Bayesian Points: -1; VCEP specifications version v2.0; 7/24/2024)
Met criteria codes
BP4
BP4 MODERATE APPLIED Computational predictor scores (BayesDel = -0.1612; Align GVGD Class C0) are below the recommended thresholds (BayesDel ≤ -0.008 and an Align GVGD Class ≤ 55), evidence that does not predict a damaging effect on TP53 via protein change. SpliceAI predicts that the variant has no impact on splicing (BP4_Moderate).
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
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
BS3
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
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
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
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
PM1
This variant does not reside within a region of TP53 that is defined as a mutational hotspot by the ClinGen TP53 VCEP (PM1 not met).
PM5
3 different missense variants (c.206C>T, p.Ala69Val ; c.205G>C, p.Ala69Pro ; c.205G>A, p.Ala69Thr) in the same codon have been reported (ClinVar Variation IDs: 528260, 919370 575773). However, these variants have not yet met the criteria to be classified as pathogenic or likely pathogenic by the ClinGen TP53 VCEP’s specifications (PM5 not met).
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