Submissions for variant NM_000546.6(TP53):c.216C>T (p.Pro72=)

gnomAD frequency: 0.00022  dbSNP: rs56275308

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163616	SCV000214183	likely benign	Hereditary cancer-predisposing syndrome	2014-07-14	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081606	SCV000253308	likely benign	Li-Fraumeni syndrome	2025-01-23	criteria provided, single submitter	clinical testing
GeneDx	RCV000444926	SCV000516188	benign	not specified	2015-04-30	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health	RCV000163616	SCV000686728	likely benign	Hereditary cancer-predisposing syndrome	2016-06-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589597	SCV000697437	benign	not provided	2017-04-27	criteria provided, single submitter	clinical testing	Variant summary: The TP53 c.216C>T (p.Pro72Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 7/120822 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.000602 (6/9970). This frequency is about 15 times the estimated maximal expected allele frequency of a pathogenic TP53 variant (0.0000398), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Genetic Services Laboratory, University of Chicago	RCV000444926	SCV002070803	likely benign	not specified	2019-06-14	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163616	SCV002530434	benign	Hereditary cancer-predisposing syndrome	2021-11-26	criteria provided, single submitter	curation
Genome-Nilou Lab	RCV000163616	SCV002582276	likely benign	Hereditary cancer-predisposing syndrome	2022-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002288721	SCV002582938	likely benign	Li-Fraumeni syndrome 1	2022-06-18	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV002288721	SCV004015641	benign	Li-Fraumeni syndrome 1	2023-07-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001081606	SCV004823831	likely benign	Li-Fraumeni syndrome	2023-12-01	criteria provided, single submitter	clinical testing