ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.993+12T>C (rs1800899)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics 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: 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,PreventionGenetics RCV000079206 SCV000305122 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,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 Health, Inc 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
Invitae RCV001518058 SCV001726688 benign Li-Fraumeni syndrome 2020-12-04 criteria provided, single submitter clinical testing
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.

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