ClinVar Miner

Submissions for variant NM_000077.4(CDKN2A):c.149A>G (p.Gln50Arg) (rs587778189)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213788 SCV000276403 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Good segregation with disease (lod 1.5-3 = 5-9 meioses),Other strong data supporting pathogenic classification
Color RCV000213788 SCV000689580 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-08 criteria provided, single submitter clinical testing
Database of Curated Mutations (DoCM) RCV000431578 SCV000505917 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442170 SCV000505918 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424913 SCV000505919 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437789 SCV000505920 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442244 SCV000505921 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427856 SCV000505922 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438067 SCV000505923 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Invitae RCV000471227 SCV000545524 uncertain significance Hereditary cutaneous melanoma 2016-12-06 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 50 of the CDKN2A protein (p.Gln50Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with melanoma (PMID: 11477665) and segregates with melanoma in a single large family (PMID: 8595405, 11500805). This variant has also been reported in an individual affected with pancreatic cancer (PMID: 25356972). In the literature, this variant is also known as 143A>G (Gln42Arg). ClinVar contains an entry for this variant (Variation ID: 232304). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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