ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.249C>G (p.His83Gln)

dbSNP: rs34968276
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002429347 SCV002742662 pathogenic Hereditary cancer-predisposing syndrome 2022-07-05 criteria provided, single submitter clinical testing The p.H83Q pathogenic mutation (also known as c.249C>G), located in coding exon 2 of the CDKN2A gene, results from a C to G substitution at nucleotide position 249. The histidine at codon 83 is replaced by glutamine, an amino acid with highly similar properties. Another alteration at the same codon, p.H83Q (c.249C>A) resulting in the same amino acid change, has been reported in multiple individuals with melanoma as well as an Italian familial melanoma kindred (Begg CB et al. J Natl Cancer Inst. 2005 Oct 19;97(20):1507-15; Berwick M et al. Cancer Epidemiol Biomarkers Prev. 2006 Aug;15(8):1520-5; Orlow I et al. J Invest Dermatol. 2007 May;127(5):1234-43; Pedace L et al. Cancer Epidemiol. 2011 Dec;35(6):e116-20; Ambry internal data). This amino acid position is highly conserved in available vertebrate species. This alteration disrupts the ankyrin domain near its interface with kinases (Russo AA. et al. Nature.1998 Sep;395(6699):237-43; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Database of Curated Mutations (DoCM) RCV000423602 SCV000505890 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431254 SCV000505891 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441491 SCV000505892 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422956 SCV000505893 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433889 SCV000505894 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443430 SCV000505895 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422116 SCV000505896 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432376 SCV000505897 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only

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