ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.273G>A (p.Leu91=)

gnomAD frequency: 0.00054  dbSNP: rs4987127
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080130 SCV000283441 likely benign Familial melanoma 2020-11-30 criteria provided, single submitter clinical testing
GeneDx RCV000656828 SCV000292538 uncertain significance not provided 2022-10-12 criteria provided, single submitter clinical testing In silico analysis supports a deleterious effect on protein structure/function; This variant in the p14-ARF isoform also results in a likely benign variant in the p16 protein, p.(Leu91=); Reported using an alternate transcript of the gene; This variant is associated with the following publications: (PMID: 27527004, 28223509, 25318351, 27473757, 24728327, 28410231)
Counsyl RCV000411786 SCV000488927 likely benign Melanoma-pancreatic cancer syndrome 2016-07-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000570074 SCV000669172 likely benign Hereditary cancer-predisposing syndrome 2015-05-06 criteria provided, single submitter clinical testing In silico models in agreement (benign);Synonymous alterations with insufficient evidence to classify as benign
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000656828 SCV000888051 benign not provided 2019-01-25 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000570074 SCV000910849 likely benign Hereditary cancer-predisposing syndrome 2016-03-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000120545 SCV000917152 benign not specified 2018-12-14 criteria provided, single submitter clinical testing Variant summary: CDKN2A c.273G>A alters a conserved nucleotide resulting in a synonymous change. One of two in-silico tools predict a benign effect of the variant on protein function. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00011 in 262192 control chromosomes, predominantly at a frequency of 0.0011 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 3.67 fold of the estimated maximal expected allele frequency for a pathogenic variant in CDKN2A causing Cutaneous Malignant Melanoma phenotype (0.0003), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. c.273G>A has been reported in the literature. These report(s) do not provide unequivocal conclusions about association of the variant with Cutaneous Malignant Melanoma. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
Genetic Services Laboratory,University of Chicago RCV000120545 SCV002070728 uncertain significance not specified 2019-05-30 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000570074 SCV002534325 likely benign Hereditary cancer-predisposing syndrome 2021-07-15 criteria provided, single submitter curation
ITMI RCV000120545 SCV000084699 not provided not specified 2013-09-19 no assertion provided reference population

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