Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166374 | SCV000217165 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-11-14 | criteria provided, single submitter | clinical testing | The p.A77P variant (also known as c.229G>C), located in coding exon 2 of the CDKN2A gene, results from a G to C substitution at nucleotide position 229 of the p14 protein-encoding isoform. The alanine at codon 77 is replaced by proline, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6286 samples (12572 alleles) with coverage at this position.<span data-redactor="verified" style="background-color: initial;">To date, this alteration has been detected with an allele frequency of approximately 0.03% (greater than 3200 alleles tested) in our clinical cohort.<span data-redactor="verified" style="background-color: initial;">This amino acid position is not well conserved in available vertebrate species, and proline is the reference amino acid in several mammals. In addition, the in silico prediction for this alteration is inconclusive.<span data-redactor="verified" style="background-color: initial;">Since supporting evidence is limited at this time, the clinical significance of p.A77P remains unclear. |