Submissions for variant NM_000546.6(TP53):c.993+12T>C

gnomAD frequency: 0.01614  dbSNP: rs1800899

Total submissions: 30

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079206	SCV000111076	benign	not specified	2013-01-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000130599	SCV000185473	benign	Hereditary cancer-predisposing syndrome	2014-11-18	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Vantari Genetics	RCV000130599	SCV000267093	benign	Hereditary cancer-predisposing syndrome	2016-02-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079206	SCV000305122	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000610122	SCV000407068	benign	Li-Fraumeni syndrome 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Diagnostics, LLC DBA Color Health	RCV000130599	SCV000537363	benign	Hereditary cancer-predisposing syndrome	2015-03-31	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000130599	SCV000679747	likely benign	Hereditary cancer-predisposing syndrome	2017-07-12	criteria provided, single submitter	clinical testing
Counsyl	RCV000610122	SCV000785578	benign	Li-Fraumeni syndrome 1	2017-09-22	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000079206	SCV001158789	benign	not specified	2018-08-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001518058	SCV001726688	benign	Li-Fraumeni syndrome	2025-02-04	criteria provided, single submitter	clinical testing
GeneDx	RCV001650902	SCV001867329	benign	not provided	2018-11-29	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30796655, 26270727)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798278	SCV002042839	benign	Breast and/or ovarian cancer	2021-05-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001650902	SCV002498234	benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	TP53: BS1, BS2
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225283	SCV002505063	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV002225283	SCV002515182	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000130599	SCV002532733	benign	Hereditary cancer-predisposing syndrome	2020-05-10	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000079206	SCV002550903	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000130599	SCV002582230	likely benign	Hereditary cancer-predisposing syndrome	2022-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000610122	SCV002582792	likely benign	Li-Fraumeni syndrome 1	2022-06-18	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000610122	SCV004015624	benign	Li-Fraumeni syndrome 1	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001650902	SCV005218650	likely benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000079206	SCV000692061	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000610122	SCV000733708	benign	Li-Fraumeni syndrome 1		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357901	SCV001553501	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The TP53 c.993+12T>C, variant was not identified in the literature nor was it identified in the Genesight-COGR, Cosmic, LOVD 3.0, IARC TP53 Database, UMD TP52 Mutation Database, Database of germline p53 mutations, databases. The variant was identified in dbSNP (rs: 1800899) “with likely benign allele”, ClinVar (5x as benign and 1x as likely benign) associated with the phenotypes of Li-Fraumeni syndrome and Hereditary cancer-predisposing syndrome, and the Clinvitae database. The variant was identified in control databases in 3159 of 277250 chromosomes at a frequency of 0.011394 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: African in 656 of 24036 chromosomes (freq: 0.027), European (Non-Finnish) in 1750 of 126732 chromosomes (freq: 0.014), South Asian in 321 of 30782 chromosomes (freq: 0.01). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000079206	SCV001809361	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000079206	SCV001906417	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001650902	SCV001927550	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079206	SCV001953299	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000079206	SCV001966014	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001650902	SCV002036085	likely benign	not provided		no assertion criteria provided	clinical testing