ClinVar Miner

Submissions for variant NM_000077.4(CDKN2A):c.318G>A (p.Val106=) (rs199888003)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000590444 SCV000166205 likely benign not provided 2019-03-01 criteria provided, single submitter clinical testing
GeneDx RCV000590444 SCV000210949 uncertain significance not provided 2018-12-18 criteria provided, single submitter clinical testing This variant is denoted CDKN2A c.361G>A at the cDNA level, p.Ala121Thr (A121T) at the protein level, and results in the change of an Alanine to a Threonine (GCG>ACG) in exon 2 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. This variant also results in a change to the p16 protein; however, that nucleotide substitution is silent (p.Val106Val) at the protein level. This variant, also reported as CDKN2A Ala162Thr, was observed in several individuals with melanoma or pancreatic cancer, several individuals with childhood leukemia, and an individual with a personal history of a Lynch syndrome-related cancer and/or polyps (Begg 2005, Erlandson 2007, Orlow 2007, McWilliams 2011, Aoude 2015, Burgstaller-Muehlbacher 2015, Grant 2015, Puig 2015, Xu 2015, Yurgelun 2015, Chaffee 2018). CDKN2A Ala121Thr was observed at an allele frequency of 0.05% (60/120,190) in individuals of European (non-Finnish) ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether CDKN2A Ala121Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000160416 SCV000214026 uncertain significance Hereditary cancer-predisposing syndrome 2014-06-10 criteria provided, single submitter clinical testing Insufficient or inconclusive evidence
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212401 SCV000601025 uncertain significance not specified 2016-10-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212401 SCV000695342 likely benign not specified 2020-09-04 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000590444 SCV000805824 uncertain significance not provided 2019-11-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590444 SCV000888053 likely benign not provided 2018-07-12 criteria provided, single submitter clinical testing
Color Health, Inc RCV000160416 SCV000902687 likely benign Hereditary cancer-predisposing syndrome 2016-05-19 criteria provided, single submitter clinical testing
Mendelics RCV000988150 SCV001137762 benign Melanoma-pancreatic cancer syndrome 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001050185 SCV001214281 likely benign Hereditary melanoma 2020-12-07 criteria provided, single submitter clinical testing

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