Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129926 | SCV000184744 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-10 | criteria provided, single submitter | clinical testing | The p.G139S variant (also known as c.415G>A), located in coding exon 2 of the CDKN2A gene, results from a G to A substitution at nucleotide position 415. The glycine at codon 139 is replaced by serine, an amino acid with similar properties. This alteration has been reported in an individual with a personal history of breast cancer (Germani A et al. J Clin Med, 2020 Sep;9:). This amino acid position is poorly conserved in available vertebrate species. 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. |
| Labcorp Genetics |
RCV000196936 | SCV000254243 | uncertain significance | Familial melanoma | 2025-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 139 of the CDKN2A (p16INK4a) protein (p.Gly139Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with CDKN2A-related cancer (PMID: 32957588). ClinVar contains an entry for this variant (Variation ID: 141419). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Color Diagnostics, |
RCV000129926 | SCV000906446 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-16 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with serine at codon 139 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 been reported in an individual affected with breast cancer (PMID: 32957588). 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. |