ClinVar Miner

Submissions for variant NM_000077.4(CDKN2A):c.-19413C>G (rs528789830)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255508 SCV000322018 uncertain significance not specified 2016-07-06 criteria provided, single submitter clinical testing This variant is denoted CDKN2A c.92C>G at the cDNA level, p.Thr31Arg (T31R) at the protein level, and results in the change of a Threonine to an Arginine (ACG>AGG) of the p14-ARF protein. Of note, the CDKN2A gene encodes the p16 protein, and using an alternate reading frame, the p14-ARF protein as well. As these two proteins only share exon 2 of the CDKN2A gene, CDKN2A Thr31Arg will not affect the p16 protein. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. CDKN2A Thr31Arg was not observed at a significant allele frequency in the populations in 1000 Genomes (McVean 2012). Since Threonine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. CDKN2A Thr31Arg occurs at a position that is not conserved and is located in the region of interaction with CDK5RAP3 and MDM2 (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether CDKN2A Thr31Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000255508 SCV000601035 uncertain significance not specified 2017-03-09 criteria provided, single submitter clinical testing
Invitae RCV000535017 SCV000637447 likely benign Hereditary melanoma 2020-11-03 criteria provided, single submitter clinical testing
Counsyl RCV000663088 SCV000786183 uncertain significance Melanoma-pancreatic cancer syndrome 2018-03-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV001019130 SCV001180453 likely benign Hereditary cancer-predisposing syndrome 2019-12-19 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification

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