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

Variant: NM_001126112.2(TP53):c.214_215delinsTG (p.Pro72Cys)

CA000069

182953 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: b7e523bb-93f5-4505-943a-3286739499c5
Approved on: 2025-02-06
Published on: 2025-02-07

HGVS expressions

NM_001126112.2:c.214_215delinsTG
NM_001126112.2(TP53):c.214_215delinsTG (p.Pro72Cys)
NC_000017.11:g.7676154_7676155delinsCA
CM000679.2:g.7676154_7676155delinsCA
NC_000017.10:g.7579472_7579473delinsCA
CM000679.1:g.7579472_7579473delinsCA
NC_000017.9:g.7520197_7520198delinsCA
NG_017013.2:g.16396_16397delinsTG
ENST00000503591.2:c.214_215delinsTG
ENST00000508793.6:c.214_215delinsTG
ENST00000509690.6:c.-21-919_-21-918delinsTG
ENST00000514944.6:c.96+227_96+228delinsTG
ENST00000604348.6:c.214_215delinsTG
ENST00000269305.9:c.214_215delinsTG
ENST00000269305.8:c.214_215delinsTG
ENST00000359597.8:c.214_215delinsTG
ENST00000413465.6:c.214_215delinsTG
ENST00000420246.6:c.214_215delinsTG
ENST00000445888.6:c.214_215delinsTG
ENST00000455263.6:c.214_215delinsTG
ENST00000503591.1:c.214_215delinsTG
ENST00000505014.5:n.470_471delinsTG
ENST00000508793.5:c.214_215delinsTG
ENST00000509690.5:c.-21-919_-21-918delinsTG
ENST00000514944.5:c.96+227_96+228delinsTG
ENST00000604348.5:c.214_215delinsTG
ENST00000610292.4:c.97_98delinsTG
ENST00000610538.4:c.97_98delinsTG
ENST00000615910.4:c.214_215delinsTG
ENST00000617185.4:c.214_215delinsTG
ENST00000619485.4:c.97_98delinsTG
ENST00000620739.4:c.97_98delinsTG
ENST00000622645.4:c.97_98delinsTG
ENST00000635293.1:c.97_98delinsTG
NM_000546.5:c.214_215delinsTG
NM_001126113.2:c.214_215delinsTG
NM_001126114.2:c.214_215delinsTG
NM_001126118.1:c.97_98delinsTG
NM_001276695.1:c.97_98delinsTG
NM_001276696.1:c.97_98delinsTG
NM_001276760.1:c.97_98delinsTG
NM_001276761.1:c.97_98delinsTG
NM_001276695.2:c.97_98delinsTG
NM_001276696.2:c.97_98delinsTG
NM_001276760.2:c.97_98delinsTG
NM_001276761.2:c.97_98delinsTG
NM_000546.6:c.214_215delinsTG
NM_001126112.3:c.214_215delinsTG
NM_001126113.3:c.214_215delinsTG
NM_001126114.3:c.214_215delinsTG
NM_001126118.2:c.97_98delinsTG
NM_001276695.3:c.97_98delinsTG
NM_001276696.3:c.97_98delinsTG
NM_001276760.3:c.97_98delinsTG
NM_001276761.3:c.97_98delinsTG
More

Uncertain Significance

Met criteria codes 1
PM2_Supporting
Not Met criteria codes 20
BA1 BS2 BS4 BS3 BS1 BP3 BP2 BP4 BP7 PS2 PS4 PS3 PS1 PP1 PP3 PM4 PM1 PM5 PM6 PVS1

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 2.2.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
The NM_000546.6: c.214_215delinsTG variant in TP53 is a deletion/insertion variant predicted to cause substitution of proline by cysteine at amino acid 72 (p.Pro72Cys). Although this variant has been observed in germline cases, to our knowledge, this variant has not been reported in individuals meeting classical LFS or Chompret criteria (PS4 not met; Internal lab contributors). This variant has been observed in 4-7 heterozygous unrelated females from the same data source with no personal history of cancer prior to age 60 years and no personal history of sarcoma at any age (BS2_Moderate; Internal lab contributors). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as variant of uncertain clinical significance for Li Fraumeni syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: BS2_Moderate, PM2_Supporting. (Bayesian Points: -1; VCEP specifications version 2.2; 2/6/2025).
Met criteria codes
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
BS2_MODERATE This variant has been observed in 4-7 heterozygous unrelated females from the same data source with no personal history of cancer prior to age 60 years and no personal history of sarcoma at any age (BS2_Moderate; Internal lab contributors).
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No data
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
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
No predictions available: https://tp53.cancer.gov/mut_details?mut_id=22552 No impact with SpliceAI: https://spliceailookup.broadinstitute.org/#variant=NM_000546.6(TP53)%3Ac.214_215delinsTG%20(p.Pro72Cys)&hg=38&bc=basic&distance=500&mask=0&ra=0
BP7
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
Although this variant has been observed in germline cases, to our knowledge, this variant has not been reported in individuals meeting classical LFS or Chompret criteria (PS4 not met; Internal lab contributors)
PS3
No data.
PS1
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
PM4
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
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
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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