Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000470551 | SCV000545547 | uncertain significance | Familial melanoma | 2018-08-31 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CDKN2A-related disease. This sequence change replaces glutamic acid with glutamine at codon 2 of the CDKN2A protein (p.Glu2Gln). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and glutamine. |
Ambry Genetics | RCV002339143 | SCV002644510 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-02 | criteria provided, single submitter | clinical testing | The p.E2Q variant (also known as c.4G>C), located in coding exon 1 of the CDKN2A gene, results from a G to C substitution at nucleotide position 4. The glutamic acid at codon 2 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved on limited sequence alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV002339143 | SCV004361324 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-15 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glutamine at codon 2 of the CDKN2A (p16INK4A) protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |