ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.316G>A (p.Val106Met)

dbSNP: rs775860099
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001882137 SCV002167310 uncertain significance Familial melanoma 2021-07-02 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that p.Val106Met does not substantially affect CDKN2A (p16INK4a) protein function (PMID: 9053859). In addition, experimental studies have shown that p.Arg120His does not substantially affect CDKN2A (p14ARF) protein function (PMID: 9366518) Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of p.Val106Met in p16INK4a (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0") or on the effect of p.Arg120His in p14ARF (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 106 of the CDKN2A (p16INK4a) protein (p.Val106Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. Alternatively, this sequence change replaces arginine with histidine at codon 120 of the CDKN2A (p14ARF) protein (p.Arg120His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. The CDKN2A gene encodes two different proteins, p16INK4a and p14ARF, which are translated from alternative transcripts that have different open reading frames.

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