Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002424165 | SCV002730352 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2016-02-04 | criteria provided, single submitter | clinical testing | The p.D70V variant (also known as c.209A>T), located in coding exon 3 of the PMS2 gene, results from an A to T substitution at nucleotide position 209. The aspartic acid at codon 70 is replaced by valine, an amino acid with highly dissimilar 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 6497 samples (12994 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 150000 alleles tested) in our clinical cohort. The p.D70V alteration has been observed in an individual with features consistent with constitutional mismatch repair deficiency (CMMR-D) who was also heterozygous for a PMS2 gross deletion in trans (Internal Ambry data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |