Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000579546 | SCV000684517 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-24 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000579546 | SCV001175779 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-20 | criteria provided, single submitter | clinical testing | The p.A76T variant (also known as c.226G>A), located in coding exon 2 of the CDKN2A gene, results from a G to A substitution at nucleotide position 226. The alanine at codon 76 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001303573 | SCV001492822 | uncertain significance | Familial melanoma | 2024-05-31 | criteria provided, single submitter | clinical testing | The CDKN2A gene encodes two different proteins, p16INK4a and p14ARF, which are translated from alternative transcripts with different open reading frames. Both transcripts have been analyzed. We report either the variant with the higher classification or default to the CDKN2A (p16INK4a) variant. This report therefore includes the details for the CDKN2A (p16INK4a) variant. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 76 of the CDKN2A (p16INK4a) protein (p.Ala76Thr). This variant is present in population databases (rs774633329, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. This variant is also known as c.269G>A (p.Arg90His) in the CDKN2A (p14ARF) transcript. ClinVar contains an entry for this variant (Variation ID: 489866). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005056235 | SCV005727168 | uncertain significance | not specified | 2024-11-04 | criteria provided, single submitter | clinical testing | Variant summary: CDKN2A c.226G>A (p.Ala76Thr) results in a non-conservative amino acid change located in the ankyrin repeat domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.9e-05 in 214230 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.226G>A in the germline of individuals affected with Cutaneous Malignant Melanoma, Pancreatic Cancer/melanoma Syndrome, or Pancreatic Cancer and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 489866). Based on the evidence outlined above, the variant was classified as uncertain significance. |