ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.673-2A>G (rs1555525585)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785307 SCV000923875 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000553068 SCV000629851 pathogenic Li-Fraumeni syndrome 2017-03-21 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 6 of the TP53 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has been reported in the literature in individuals with suspected Li-Fraumeni syndrome (PMID: 21059199, 26029016). In one of these individuals, the variant likely arose de novo (PMID: 26029016). Experimental studies that examined the effect of this variant on TP53 function are conflicting. One study suggests that this variant causes nonsense-mediated decay of the mRNA from this allele (PMID: 24835311), while another study suggests that usage of a cryptic splice acceptor in intro 6 results in a truncated TP53 protein lacking DNA-binding and transactivation activity (PMID: 25074920). However, in either case the TP53 protein is disrupted. For these reasons, this variant has been classified as Pathogenic.
MutSpliceDB: a database of splice sites variants effects on splicing,NIH RCV000786824 SCV000925718 not provided not provided no assertion provided in vitro

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