17-7674237-G-T
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000546.6(TP53):c.726C>A(p.Cys242*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. C242C) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000546.6 stop_gained
Scores
Clinical Significance
Conservation
Publications
- breast cancerInheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
- Li-Fraumeni syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
- Li-Fraumeni syndrome 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp
- adrenocortical carcinoma, hereditaryInheritance: AD Classification: STRONG Submitted by: Ambry Genetics
- sarcomaInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- bone marrow failure syndrome 5Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
- colorectal cancerInheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
- choroid plexus carcinomaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Li-Fraumeni syndrome Pathogenic:1
This variant has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 20127978). This sequence change creates a premature translational stop signal (p.Cys242*) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at